Physical Impairments Associated with Diseases: A Pathophysiological Approach

  • Vignesh Kotian
  • Leela Mounica
  • Deepaneeta Sarmah
  • Harpreet Kaur
  • Geetesh Verma
  • Radhika Kesharwani
  • Pabbala Veeresh
  • Anupom Borah
  • Kiran Kalia
  • Pallab BhattacharyaEmail author


Today with the advent of chronic illnesses, disability associated with it has found its place as a major contributor to the global burden by impacting lives in all age groups in both developed and developing nations. “Disabilities” roots lie not just in terms of restriction in physical aspects of the patient but also in the context of social, emotional, and mental state too. With an ever-growing aging population prone to disabilities, it is quintessential today to understand the etiology and progression of diseases leading to disability. This chapter aims to focus on the pathogenesis of disease that is likely to cause disability as per the medical and social models of disability.


Disability Musculoskeletal disorder Neuropsychiatric disorder Cancer Diabetes Cardiovascular disorders 


  1. A. D. Association (2014) Diagnosis and classification of diabetes mellitus. Diabetes Care 37:S81–S90CrossRefGoogle Scholar
  2. Adams JM, Cory S (2007) The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26:1324CrossRefPubMedPubMedCentralGoogle Scholar
  3. Adelman G, Rane SG, Villa KF (2013) The cost burden of multiple sclerosis in the United States: a systematic review of the literature. J Med Econ 16:639–647CrossRefGoogle Scholar
  4. Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J et al (2013) Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol.
  5. Ahlsiö B, Britton M, Murray V, Theorell T (1984) Disablement and quality of life after stroke. Stroke 15:886–890CrossRefGoogle Scholar
  6. Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, Aimoto S et al (2010) Structural conversion of neurotoxic amyloid-β 1–42 oligomers to fibrils. Nat Struct Mol Biol 17:561CrossRefPubMedPubMedCentralGoogle Scholar
  7. Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl M-C, Nemesh J et al (2000) The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26:76CrossRefGoogle Scholar
  8. Alzhelmer A (1907) Uber eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatr 64:146–148Google Scholar
  9. Androdias G, Reynolds R, Chanal M, Ritleng C, Confavreux C, Nataf S (2010) Meningeal T cells associate with diffuse axonal loss in multiple sclerosis spinal cords. Ann Neurol 68:465–476CrossRefGoogle Scholar
  10. Bartus RT, Dean RR, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–414CrossRefGoogle Scholar
  11. Bellenguez C, Bevan S, Gschwendtner A, Spencer CC, Burgess AI, Pirinen M et al (2012) Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet 44:328CrossRefGoogle Scholar
  12. Bermel RA, Bakshi R (2006) The measurement and clinical relevance of brain atrophy in multiple sclerosis. Lancet Neurol 5:158–170CrossRefGoogle Scholar
  13. Bhowmick NA, Neilson EG, Moses HL (2004) Stromal fibroblasts in cancer initiation and progression. Nature 432:332CrossRefPubMedPubMedCentralGoogle Scholar
  14. Biffi A, Sonni A, Anderson CD, Kissela B, Jagiella JM, Schmidt H et al (2010) Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol 68:934–943CrossRefPubMedPubMedCentralGoogle Scholar
  15. Bjartmar C, Kidd G, Mörk S, Rudick R, Trapp BD (2000) Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 48:893–901CrossRefGoogle Scholar
  16. Bjartmar C, Wujek J, Trapp B (2003) Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 206:165–171CrossRefGoogle Scholar
  17. Bramow S, Frischer JM, Lassmann H, Koch-Henriksen N, Lucchinetti CF, Sørensen PS et al (2010) Demyelination versus remyelination in progressive multiple sclerosis. Brain 133:2983–2998CrossRefGoogle Scholar
  18. Brenner BM, Cooper ME, De Zeeuw D, Keane WF, Mitch WE, Parving H-H et al (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869CrossRefGoogle Scholar
  19. Bretón RR, Rodríguez JCG (2012) Excitotoxicity and oxidative stress in acute ischemic stroke. In: Acute ischemic stroke. InTech, CroatiaGoogle Scholar
  20. Bromley-Brits K, Song W (2012) The role of TMP21 in trafficking and amyloid-β precursor protein (APP) processing in Alzheimer’s disease. Curr Alzheimer Res 9:411–424CrossRefGoogle Scholar
  21. Brooks G, Fahey T, Baldwin K (2005) “Exercise, disease, and disability,” exercise physiology: human bioenergetics and its applications, 4th edn. McGraw Hill: Higher Education, New York, pp 649–680Google Scholar
  22. Brown PO, Botstein D (1999) Exploring the new world of the genome with DNA microarrays. Nat Genet 21:33CrossRefGoogle Scholar
  23. Brownell B, Hughes JT (1962) The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol, Neurosurg, Psychiatry 25:315CrossRefGoogle Scholar
  24. Bruijn L, Beal M, Becher M, Schulz J, Wong P, Price D et al (1997) Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant. Proc Natl Acad Sci 94:7606–7611CrossRefGoogle Scholar
  25. Burr D (2003) Subchondral bone in the pathogenesis of osteoarthritis. Mechanical aspects. In: Osteoarthritis. Oxford University Press, Oxford, pp 125–133Google Scholar
  26. Cade WT (2008) Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 88:1322–1335CrossRefPubMedPubMedCentralGoogle Scholar
  27. Catrina AI, Joshua V, Klareskog L, Malmström V (2016) Mechanisms involved in triggering rheumatoid arthritis. Immunol Rev 269:162–174CrossRefGoogle Scholar
  28. Chaudhury PK, Deka K, Chetia D (2006) Disability associated with mental disorders. Indian J Psychiatr 48:95CrossRefGoogle Scholar
  29. Cheng N, Chytil A, Shyr Y, Joly A, Moses HL (2008) Transforming growth factor-β signaling–deficient fibroblasts enhance hepatocyte growth factor signaling in mammary carcinoma cells to promote scattering and invasion. Mol Cancer Res 6:1521–1533CrossRefPubMedPubMedCentralGoogle Scholar
  30. Chilelli N, Burlina S, Lapolla A (2013) AGEs, rather than hyperglycemia, are responsible for microvascular complications in diabetes: a “glycoxidation-centric” point of view. Nutr Metab Cardiovasc Dis 23:913–919CrossRefGoogle Scholar
  31. Chio A, Benzi G, Dossena M, Mutani R, Mora G (2005) Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain 128:472–476CrossRefGoogle Scholar
  32. Choi SR, Howell OW, Carassiti D, Magliozzi R, Gveric D, Muraro PA et al (2012) Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis. Brain 135:2925–2937CrossRefGoogle Scholar
  33. Cox PA, Sacks OW (2002) Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam. Neurology 58:956–959CrossRefGoogle Scholar
  34. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M et al (2014) The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 73:1323–1330CrossRefPubMedPubMedCentralGoogle Scholar
  35. Cummings JL, Arciniegas DB, Brooks BR, Herndon RM, Lauterbach EC, Pioro EP et al (2006) Defining and diagnosing involuntary emotional expression disorder. CNS Spectr 11:1–11CrossRefGoogle Scholar
  36. D’Souza B, D’Souza V, Sowmya S, Seema G, Hemalatha C, Anu M et al (2008) A comparative study on oxidative stress and antioxidant status in ischemic stroke patients with and without diabetes. Indian J Clin Biochem 23:218CrossRefPubMedPubMedCentralGoogle Scholar
  37. Dassanayaka S, Jones SP (2015) Recent developments in heart failure. Circ Res 117:e58–e63CrossRefPubMedPubMedCentralGoogle Scholar
  38. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949CrossRefGoogle Scholar
  39. Dean J, Keshavan M (2017) The neurobiology of depression: an integrated view. Asian J Psychiatr 27:101–111CrossRefGoogle Scholar
  40. Dieppe PA, Lohmander LS (2005) Pathogenesis and management of pain in osteoarthritis. Lancet 365:965–973CrossRefGoogle Scholar
  41. Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397CrossRefPubMedPubMedCentralGoogle Scholar
  42. Druet C, Tubiana-Rufi N, Chevenne D, Rigal O, Polak M, Levy-Marchal C (2006) Characterization of insulin secretion and resistance in type 2 diabetes of adolescents. J Clin Endocrinol Metab 91:401–404CrossRefGoogle Scholar
  43. Drummond K, Mauer M (2002) The early natural history of nephropathy in type 1 diabetes: II. Early renal structural changes in type 1 diabetes. Diabetes 51:1580–1587CrossRefGoogle Scholar
  44. Du Yan S, Chen X, Fu J, Chen M, Zhu H, Roher A et al (1996) RAGE and amyloid-β peptide neurotoxicity in Alzheimer’s disease. Nature 382:685CrossRefPubMedPubMedCentralGoogle Scholar
  45. Du Yan S, Zhu H, Fu J, Yan SF, Roher A, Tourtellotte WW et al (1997) Amyloid-β peptide–receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease. Proc Natl Acad Sci 94:5296–5301CrossRefPubMedPubMedCentralGoogle Scholar
  46. Duckett L (2001) Alzheimer’s dementia: morbidity and mortality. J Insur Med (New York, NY) 33:227–234Google Scholar
  47. Dyck PJ, Kratz K, Karnes J, Litchy WJ, Klein R, Pach J et al (1993) The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 43:817–817CrossRefGoogle Scholar
  48. Eikelenboom P, Veerhuis R (1999) The importance of inflammatory mechanisms for the development of Alzheimer’s disease. Exp Gerontol 34:453–461CrossRefGoogle Scholar
  49. Feinstein A (2011) Multiple sclerosis and depression. Mult Scler J 17:1276–1281CrossRefGoogle Scholar
  50. Felger JC, Lotrich FE (2013) Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience 246:199–229CrossRefPubMedPubMedCentralGoogle Scholar
  51. Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453CrossRefPubMedPubMedCentralGoogle Scholar
  52. Figueroa MS, Peters JI (2006) Congestive heart failure: diagnosis, pathophysiology, therapy, and implications for respiratory care. Respir Care 51:403–412PubMedPubMedCentralGoogle Scholar
  53. Fischer MT, Wimmer I, Höftberger R, Gerlach S, Haider L, Zrzavy T et al (2013) Disease-specific molecular events in cortical multiple sclerosis lesions. Brain 136:1799–1815CrossRefPubMedPubMedCentralGoogle Scholar
  54. Friedberg EC (2003) DNA damage and repair. Nature 421:436CrossRefPubMedPubMedCentralGoogle Scholar
  55. Gabriel-Costa D (2018) The pathophysiology of myocardial infarction-induced heart failure. Pathophysiology 25(4):277–284CrossRefPubMedPubMedCentralGoogle Scholar
  56. Gallo V, Bueno-De-Mesquita HB, Vermeulen R, Andersen PM, Kyrozis A, Linseisen J et al (2009) Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort. Ann Neurol 65:378–385CrossRefPubMedPubMedCentralGoogle Scholar
  57. Gerstein HC (1994) Cow’s milk exposure and type I diabetes mellitus: a critical overview of the clinical literature. Diabetes Care 17:13–19CrossRefPubMedPubMedCentralGoogle Scholar
  58. Ginsberg H, Kimmerling G, Olefsky JM, Reaven GM (1975) Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia. J Clin Investig 55:454–461CrossRefPubMedPubMedCentralGoogle Scholar
  59. Goering S (2015) Rethinking disability: the social model of disability and chronic disease. Curr Rev Musculoskelet Med 8:134–138CrossRefPubMedPubMedCentralGoogle Scholar
  60. Goldring SR (2008) Targeting disease: musculoskeletal conditions. Pharm Res 25(12):2878–2880CrossRefGoogle Scholar
  61. Gray E, Paula-Barbosa M, Roher A (1987) Alzheimer’s disease: paired helical filaments and cytomembranes. Neuropathol Appl Neurobiol 13:91–110CrossRefPubMedPubMedCentralGoogle Scholar
  62. Halban PA, Polonsky KS, Bowden DW, Hawkins MA, Ling C, Mather KJ et al (2014) β-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. J Clin Endocrinol Metab 99:1983–1992CrossRefPubMedPubMedCentralGoogle Scholar
  63. Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364CrossRefPubMedPubMedCentralGoogle Scholar
  64. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRefGoogle Scholar
  65. Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184CrossRefPubMedPubMedCentralGoogle Scholar
  66. Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E et al (2012) Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Investig 122:1791–1802CrossRefPubMedPubMedCentralGoogle Scholar
  67. Harwood CA, McDermott CJ, Shaw PJ (2009) Physical activity as an exogenous risk factor in motor neuron disease (MND): a review of the evidence. Amyotroph Lateral Scler 10:191–204CrossRefPubMedPubMedCentralGoogle Scholar
  68. Heiland EG, Welmer A-K, Wang R, Santoni G, Fratiglioni L, Qiu C (2018) Cardiovascular risk factors and the risk of disability in older adults: variation by age and functional status. J Am Med Dir Assoc.
  69. Hensley K, Mhatre M, Mou S, Pye QN, Stewart C, West M et al (2006) On the relation of oxidative stress to neuroinflammation: lessons learned from the G93A-SOD1 mouse model of amyotrophic lateral sclerosis. Antioxid Redox Signal 8:2075–2087CrossRefPubMedPubMedCentralGoogle Scholar
  70. Hertel JKH, Johansson S, Midthjell K, Nygård O, Njølstad PR, Molven A (2013) Type 2 diabetes genes–Present status and data from Norwegian studies. Norsk Epidemiol 23.
  71. Hinkle JL, Guanci MM (2007) Acute ischemic stroke review. J Neurosci Nurs 39:285–293CrossRefGoogle Scholar
  72. Howell OW, Reeves CA, Nicholas R, Carassiti D, Radotra B, Gentleman SM et al (2011) Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 134:2755–2771CrossRefGoogle Scholar
  73. Hoy D, Bain C, Williams G, March L, Brooks P, Blyth F et al (2012) A systematic review of the global prevalence of low back pain. Arthritis Rheum 64:2028–2037CrossRefGoogle Scholar
  74. Inamdar A, Inamdar A (2016) Heart failure: diagnosis, management and utilization. J Clin Med 5:62CrossRefPubMedPubMedCentralGoogle Scholar
  75. Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415CrossRefGoogle Scholar
  76. Jugdutt BI (2010) Aging and heart failure: changing demographics and implications for therapy in the elderly. Heart Fail Rev 15:401–405CrossRefPubMedPubMedCentralGoogle Scholar
  77. Juhász G, Barkóczi B, Vass G, Datki Z, Hunya Á, Fülöp L et al (2010) Fibrillar Aβ 1-42 enhances NMDA receptor sensitivity via the integrin signaling pathway. J Alzheimers Dis 19:1055–1067CrossRefGoogle Scholar
  78. Jurgens CA, Toukatly MN, Fligner CL, Udayasankar J, Subramanian SL, Zraika S et al (2011) β-cell loss and β-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition. Am J Pathol 178:2632–2640CrossRefPubMedPubMedCentralGoogle Scholar
  79. Källberg H, Ding B, Padyukov L, Bengtsson C, Rönnelid J, Klareskog L et al (2011) Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke. Ann Rheum Dis 70:508–511CrossRefPubMedPubMedCentralGoogle Scholar
  80. Kanyal N (2015) The science of ischemic stroke: pathophysiology & pharmacological treatment. Int J Pharma Res Rev 4:65–84Google Scholar
  81. Kasarskis EJ, Lindquist JH, Coffman CJ, Grambow SC, Feussner JR, Allen KD et al (2009) Clinical aspects of ALS in Gulf War veterans. Amyotroph Lateral Scler 10:35–41CrossRefGoogle Scholar
  82. Kasarskis EJ, Mendiondo MS, Matthews DE, Mitsumoto H, Tandan R, Simmons Z et al (2014) Estimating daily energy expenditure in individuals with amyotrophic lateral sclerosis. Am J Clin Nutr 99:792–803CrossRefPubMedPubMedCentralGoogle Scholar
  83. Khoury JC, Kleindorfer D, Alwell K, Moomaw CJ, Woo D, Adeoye O et al (2013) Diabetes mellitus: a risk factor for ischemic stroke in a large biracial population. Stroke 44:1500–1504CrossRefPubMedPubMedCentralGoogle Scholar
  84. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O et al (2011) Amyotrophic lateral sclerosis. Lancet 377:942–955CrossRefGoogle Scholar
  85. Kilarski LL, Achterberg S, Devan WJ, Traylor M, Malik R, Lindgren A et al (2014) Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24. 12. Neurology 83:678–685CrossRefPubMedPubMedCentralGoogle Scholar
  86. Klijs B, Nusselder WJ, Looman CW, Mackenbach JP (2011) Contribution of chronic disease to the burden of disability. PLoS One 6:e25325CrossRefPubMedPubMedCentralGoogle Scholar
  87. Knudson AG (2002) Cancer genetics. Am J Med Genet 111:96–102CrossRefGoogle Scholar
  88. Konig MF, Abusleme L, Reinholdt J, Palmer RJ, Teles RP, Sampson K et al (2016) Aggregatibacter actinomycetemcomitans–induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med 8:369ra176–369ra176CrossRefPubMedPubMedCentralGoogle Scholar
  89. Korshavn KJ, Bhunia A, Lim MH, Ramamoorthy A (2016) Amyloid-β adopts a conserved, partially folded structure upon binding to zwitterionic lipid bilayers prior to amyloid formation. Chem Commun 52:882–885CrossRefGoogle Scholar
  90. Kotler SA, Walsh P, Brender JR, Ramamoorthy A (2014) Differences between amyloid-β aggregation in solution and on the membrane: insights into elucidation of the mechanistic details of Alzheimer’s disease. Chem Soc Rev 43:6692–6700CrossRefPubMedPubMedCentralGoogle Scholar
  91. Kotler SA, Brender JR, Vivekanandan S, Suzuki Y, Yamamoto K, Monette M et al (2015) High-resolution NMR characterization of low abundance oligomers of amyloid-β without purification. Sci Rep 5:11811CrossRefPubMedPubMedCentralGoogle Scholar
  92. Krishnamurthy A, Joshua V, Hensvold AH, Jin T, Sun M, Vivar N et al (2016) Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss. Ann Rheum Dis 75:721–729CrossRefGoogle Scholar
  93. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Brück W, Rauschka H, Bergmann M et al (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712CrossRefGoogle Scholar
  94. Lassmann H, Brück W, Lucchinetti CF (2007) The immunopathology of multiple sclerosis: an overview. Brain Pathol 17:210–218CrossRefGoogle Scholar
  95. Lee Y, Lee S-R, Choi SS, Yeo H-G, Chang K-T, Lee HJ (2014) Therapeutically targeting neuroinflammation and microglia after acute ischemic stroke. BioMed Res Int 2014:297241PubMedPubMedCentralGoogle Scholar
  96. Lekander I, Willers C, Von Euler M, Lilja M, Sunnerhagen KS, Pessah-Rasmussen H et al (2017) Relationship between functional disability and costs one and two years post stroke. PloS One 12:e0174861CrossRefPubMedPubMedCentralGoogle Scholar
  97. Leonard BE (2001) Stress, norepinephrine and depression. J Psychiatry Neurosci: JPN 26:S11PubMedGoogle Scholar
  98. Lindgren A (2014) Stroke genetics: a review and update. J Stroke 16:114CrossRefPubMedPubMedCentralGoogle Scholar
  99. Lindgren P, Glader E-L, Jönsson B (2008) Utility loss and indirect costs after stroke in Sweden. Eur J Cardiovasc Prev Rehabil 15:230–233CrossRefGoogle Scholar
  100. Liu R, Althaus JS, Ellerbrock BR, Becker DA, Gurney ME (1998) Enhanced oxygen radical production in a transgenic mouse model of familial amyotrophic lateral sclerosis. Ann Neurol 44:763–770CrossRefGoogle Scholar
  101. Lloyd-Jones D, Adams R, Brown T, Carnethon M, Dai S, De Simone G et al (2010) Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 121:e46PubMedGoogle Scholar
  102. Lorenzo-Almoros A, Tunon J, Orejas M, Cortés M, Egido J, Lorenzo Ó (2017) Diagnostic approaches for diabetic cardiomyopathy. Cardiovasc Diabetol 16:28CrossRefPubMedPubMedCentralGoogle Scholar
  103. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V et al (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2095–2128CrossRefGoogle Scholar
  104. Luengo-Fernandez R, Paul NL, Gray AM, Pendlebury ST, Bull LM, Welch SJ et al (2013) Population-based study of disability and institutionalization after transient ischemic attack and stroke: 10-year results of the Oxford Vascular Study. Stroke 44:2854–2861CrossRefPubMedPubMedCentralGoogle Scholar
  105. Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ (2010) Epidemiology of type 1 diabetes. Endocrinol Metab Clin 39:481–497CrossRefGoogle Scholar
  106. Machado-Vieira R, Salvadore G, DiazGranados N, Ibrahim L, Latov D, Wheeler-Castillo C et al (2010) New therapeutic targets for mood disorders. Sci World J 10:713–726CrossRefGoogle Scholar
  107. Mahad DH, Trapp BD, Lassmann H (2015) Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 14:183–193CrossRefGoogle Scholar
  108. Maher P, Davis JB (1996) The role of monoamine metabolism in oxidative glutamate toxicity. J Neurosci 16:6394–6401CrossRefPubMedPubMedCentralGoogle Scholar
  109. Marburg O (1906) Die sogenannte akute multiple Sklerose: Рипол Классик.Google Scholar
  110. March L, Smith EU, Hoy DG, Cross MJ, Sanchez-Riera L, Blyth F et al (2014) Burden of disability due to musculoskeletal (MSK) disorders. Best Pract Res Clin Rheumatol 28:353–366CrossRefGoogle Scholar
  111. McInnes IB, Schett G (2017) Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet 389:2328–2337CrossRefGoogle Scholar
  112. Mehta S, Vemuganti R (2014) Mechanisms of stroke induced neuronal death: multiple therapeutic opportunities. Adv Anim Vet Sci 2:438–446CrossRefGoogle Scholar
  113. Meldrum B, Garthwaite J (1990) Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol Sci 11:379–387CrossRefGoogle Scholar
  114. Morris J (1996) Encounters with strangers: feminism and disability. Womens Press Ltd, LondonGoogle Scholar
  115. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C et al (2012) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2197–2223CrossRefPubMedPubMedCentralGoogle Scholar
  116. Nguyen DV, Shaw L, Grant M (2012) Inflammation in the pathogenesis of microvascular complications in diabetes. Front Endocrinol 3:170CrossRefGoogle Scholar
  117. Nickerson HD, Dutta S (2012) Diabetic complications: current challenges and opportunities. J Cardiovasc Transl Res 5:375–379CrossRefPubMedPubMedCentralGoogle Scholar
  118. Nielsen E-MD, Hansen L, Carstensen B, Echwald SM, Drivsholm T, Glümer C et al (2003) The E23K variant of Kir6. 2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes 52:573–577CrossRefGoogle Scholar
  119. Okur ME, Karantas ID, Siafaka PI (2017) Diabetes Mellitus: a review on pathophysiology, current status of oral pathophysiology, current status of oral medications and future perspectives. ACTA Pharma Sci 55:482–494Google Scholar
  120. Orogo AM, Gustafsson ÅB (2013) Cell death in the myocardium: my heart won’t go on. IUBMB Life 65:651–656CrossRefPubMedPubMedCentralGoogle Scholar
  121. Papatheodorou K, Papanas N, Banach M, Papazoglou D, Edmonds M (2016) Complications of diabetes 2016. J Diabetes Res 2016.
  122. Pasinelli P, Brown RH (2006) Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7:710CrossRefGoogle Scholar
  123. Peterson JW, Bö L, Mörk S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol Off J Am Neurol Assoc Child Neurol Soc 50:389–400Google Scholar
  124. Pociot F, Akolkar B, Concannon P, Erlich HA, Julier C, Morahan G et al (2010) Genetics of type 1 diabetes: what’s next? Diabetes 59:1561–1571CrossRefPubMedPubMedCentralGoogle Scholar
  125. Poitout V, Robertson RP (2007) Glucolipotoxicity: fuel excess and β-cell dysfunction. Endocr Rev 29:351–366CrossRefPubMedPubMedCentralGoogle Scholar
  126. Polyak K, Riggins GJ (2001) Gene discovery using the serial analysis of gene expression technique: implications for cancer research. J Clin Oncol 19:2948–2958CrossRefGoogle Scholar
  127. Pruessner M, Hellhammer DH, Pruessner JC, Lupien SJ (2003) Self-reported depressive symptoms and stress levels in healthy young men: associations with the cortisol response to awakening. Psychosom Med 65:92–99CrossRefGoogle Scholar
  128. Radunovic A, Annane D, Jewitt K, Mustfa N (2009) Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 4:CD004427Google Scholar
  129. Reimer KA, Jennings RB (1981) Energy metabolism in the reversible and irreversible phases of severe myocardial ischemia. Acta Med Scand 210:19–27CrossRefGoogle Scholar
  130. Richelson E (2001) Pharmacology of antidepressants. Mayo Clin Proc 76:511–527CrossRefGoogle Scholar
  131. Sandy J (2003) Proteolytic degradation of normal and osteoarthritic cartilage matrix. Osteoarthritis 2003:82–92Google Scholar
  132. Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C et al (2013) Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. elife 2:e01202CrossRefPubMedPubMedCentralGoogle Scholar
  133. Sharma L (2003) Local mechanical factors in the natural history of knee osteoarthritis. Malalignment and joint laxity. Osteoarthritis 2:177–183Google Scholar
  134. Silvers A (1998) A fatal attraction to normalizing: treating disabilities as deviations from ôspecies-typicalõ functioning. Enhanc Hum Traits 1998:95–123Google Scholar
  135. Soerjomataram I, Lortet-Tieulent J, Parkin DM, Ferlay J, Mathers C, Forman D et al (2012) Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet 380:1840–1850CrossRefPubMedPubMedCentralGoogle Scholar
  136. Stankowski JN, Gupta R (2011) Therapeutic targets for neuroprotection in acute ischemic stroke: lost in translation? Antioxid Redox Signal 14:1841–1851CrossRefPubMedPubMedCentralGoogle Scholar
  137. Stoll G, Kleinschnitz C, Nieswandt B (2008) Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood 112:3555–3562CrossRefPubMedPubMedCentralGoogle Scholar
  138. Sun X, Bromley-Brits K, Song W (2012) Regulation of β-site APP-cleaving enzyme 1 gene expression and its role in Alzheimer’s Disease. J Neurochem 120:62–70CrossRefPubMedPubMedCentralGoogle Scholar
  139. Supnet C, Bezprozvanny I (2010) The dysregulation of intracellular calcium in Alzheimer disease. Cell Calcium 47:183–189CrossRefPubMedPubMedCentralGoogle Scholar
  140. Sutedja NA, Veldink JH, Fischer K, Kromhout H, Heederik D, Huisman MH et al (2009) Exposure to chemicals and metals and risk of amyotrophic lateral sclerosis: a systematic review. Amyotroph Lateral Scler 10:302–309CrossRefGoogle Scholar
  141. Suzuki Y, Brender JR, Soper MT, Krishnamoorthy J, Zhou Y, Ruotolo BT et al (2013) Resolution of oligomeric species during the aggregation of Aβ1–40 using 19F NMR. Biochemistry 52:1903–1912CrossRefPubMedPubMedCentralGoogle Scholar
  142. Swerdlow RH, Khan SM (2004) A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease. Med Hypotheses 63:8–20CrossRefPubMedPubMedCentralGoogle Scholar
  143. Talmadge JE, Fidler IJ (2010) AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res 70:0008–5472. CAN-10-1040CrossRefGoogle Scholar
  144. Tõugu V, Tiiman A, Palumaa P (2011) Interactions of Zn (II) and Cu (II) ions with Alzheimer’s amyloid-beta peptide. Metal ion binding, contribution to fibrillization and toxicity. Metallomics 3:250–261CrossRefPubMedPubMedCentralGoogle Scholar
  145. Traylor M, Farrall M, Holliday EG, Sudlow C, Hopewell JC, Cheng Y-C et al (2012) Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. Lancet Neurol 11:951–962CrossRefPubMedPubMedCentralGoogle Scholar
  146. Van den Berg W, Van der Kraan P, Van Beuningen H (2003) Synovial mediators of cartilage damage and repair in osteoarthritis. In: Brandt KD, Doherty M, Lohmander LS (eds) Osteoarthritis, 2nd edn. Oxford University Press, Oxford, pp 147–155Google Scholar
  147. Ventura-Clapier R, Garnier A, Veksler V, Joubert F (2011) Bioenergetics of the failing heart. Biochim Biophys Acta (BBA)-Mol Cell Res 1813:1360–1372CrossRefGoogle Scholar
  148. Vinik AI, Maser RE, Mitchell BD, Freeman R (2003) Diabetic autonomic neuropathy. Diabetes Care 26:1553–1579CrossRefPubMedPubMedCentralGoogle Scholar
  149. Vucic S, Kiernan MC (2009) Pathophysiology of neurodegeneration in familial amyotrophic lateral sclerosis. Curr Mol Med 9:255–272CrossRefPubMedPubMedCentralGoogle Scholar
  150. W. H. Organization (2001) International Classification of Impairment, Disability and Handicap (ICIDH-2 beta version). WHO Website, 1999, Available at (Accessed): Date: June, 2001
  151. Weinberg R, Hanahan D (2000) The hallmarks of cancer. Cell 100:57–70CrossRefPubMedPubMedCentralGoogle Scholar
  152. Williamson TL, Cleveland DW (1999) Slowing of axonal transport is a very early event in the toxicity of ALS–linked SOD1 mutants to motor neurons. Nat Neurosci 2:50CrossRefPubMedPubMedCentralGoogle Scholar
  153. Wu N, Minden SL, Hoaglin DC, Hadden L, Frankel D (2007) Quality of life in people with multiple sclerosis: data from the Sonya Slifka Longitudinal Multiple Sclerosis Study. J Health Hum Serv Adm 30:233–267PubMedGoogle Scholar
  154. Zanetti O, Bianchetti A, Frisoni GB, Rozzini R, Trabucchi M (1993) Determinants of disability in Alzheimer’s disease. Int J Geriatric Psychiatr 8:581–586CrossRefGoogle Scholar
  155. Zeitler P (2009) Update on nonautoimmune diabetes in children. J Clin Endocrinol Metab 94:2215–2220CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Vignesh Kotian
    • 1
  • Leela Mounica
    • 1
  • Deepaneeta Sarmah
    • 1
  • Harpreet Kaur
    • 1
  • Geetesh Verma
    • 1
  • Radhika Kesharwani
    • 1
  • Pabbala Veeresh
    • 1
  • Anupom Borah
    • 2
  • Kiran Kalia
    • 1
  • Pallab Bhattacharya
    • 1
    Email author
  1. 1.Department of Pharmacology and ToxicologyNational Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A)GandhinagarIndia
  2. 2.Department of Life Science and BioinformaticsAssam UniversitySilcharIndia

Personalised recommendations