Skip to main content

Neurodegeneration

  • Chapter
  • First Online:
Neuroimmune Pharmacology

Abstract

Neurodegeneration is any pathological condition in which the nervous system or nerve cell (i.e. neuron) loses its function, structure, or both. On a medical point of view however, the term neurodegeneration is used in a more restricted sense. Typically, it represents a large group of heterogeneous disorders in which affected neurons belong to specific subtypes, within specific anatomofunctional territories of the nervous system. Often, but not always neurodegenerative diseases arise for unknown reasons and progress in a relentless manner. Within the context of this definition diseases of the nervous system can be catalogued into three board categories: (i) pathologies which are restricted to the nervous system and which are primary neuronal diseases (i.e. neurodegenerative diseases per se); (ii) pathologies which are restricted to the nervous system but are not primary neuronal diseases, such as brain neoplasm or cerebral edema and hemorrhage; and, (iii) pathologies provoked by systemic causes which damage the nervous system, such cardiovascular arrest, carbon monoxide poison, or infections due to herpes simplex. Based on this simple categorization, hundreds of disorders of the nervous system including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis clearly fulfill the criteria of neurodegenerative disorder and are unanimously regarded as such.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bjartmar C, Wujek JR, Trapp BD (2003) Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 206(2):165–171

    Article  CAS  PubMed  Google Scholar 

  • Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211

    Article  PubMed  Google Scholar 

  • Casals J, Elizan TS, Yahr MD (1998) Postencephalitic Parkinsonism—a review. J Neural Transm 105(6-7):645–676

    Article  CAS  PubMed  Google Scholar 

  • Chen K-M, Chase TN (1986) Parkinsonism-dementia. In: Vinken PJ, Bruyn GW, Klawans HL (eds) Handbook of clinical neurology, vol 49, Extrapyramidal disorders. Elsevier, Amsterdam, pp 167–183

    Google Scholar 

  • Chen H, Zhang SM, Hernan MA, Schwarzschild MA, Willett WC, Colditz GA, Speizer FE, Ascherio A (2003) Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol 60(8):1059–1064

    Article  PubMed  Google Scholar 

  • Clarke PGH, Oppenheim RW (1995) Neuron death in vertebrate development: in vitro methods. Methods Cell Biol 46:277–321

    Article  CAS  PubMed  Google Scholar 

  • Clement AM, Nguyen MD, Roberts EA, Garcia ML, Boillee S, Rule M, McMahon AP, Doucette W, Siwek D, Ferrante RJ, Brown RH Jr, Julien JP, Goldstein LSB, Cleveland DW (2003) Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 302(5642):113–117

    Article  CAS  PubMed  Google Scholar 

  • Cummings CJ, Zoghbi HY (2000) Trinucleotide repeats: mechanisms and pathophysiology. Annu Rev Genomics Hum Genet 1:281–328

    Article  CAS  PubMed  Google Scholar 

  • Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39(6):889–909

    Article  CAS  PubMed  Google Scholar 

  • DeGiorgio LA, Dibinis C, Milner TA, Saji M, Volpe BT (1998) Histological and temporal characteristics of nigral transneuronal degeneration after striatal injury. Brain Res 795(1–2):1–9

    Article  CAS  PubMed  Google Scholar 

  • Doraiswamy PM, Leon J, Cummings JL, Marin D, Neumann PJ (2002) Prevalence and impact of medical comorbidity in Alzheimer’s disease. J Gerontol A Biol Sci Med Sci 57(3):M173–M177

    Article  PubMed  Google Scholar 

  • Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, Padmanabhan A, Clay-Falcone D, McCluskey L, Elman L, Juhr D, Gruber PJ, Rub U, Auburger G, Trojanowski JQ, Lee VM, Van Deerlin VM, Bonini NM, Gitler AD (2010) Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 466(7310):1069–1075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galvin JE, Lee VM, Trojanowski JQ (2001) Synucleinopathies: clinical and pathological implications. Arch Neurol 58(2):186–190

    Article  CAS  PubMed  Google Scholar 

  • Garden GA, La Spada AR (2012) Intercellular (mis)communication in neurodegenerative disease. Neuron 73(5):886–901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ginsberg SD, Martin LJ (2002) Axonal transection in adult rat brain induces transsynaptic apoptosis and persistent atrophy of target neurons. J Neurotrauma 19(1):99–109

    Article  PubMed  Google Scholar 

  • Goedert M, Spillantini MG (2001) Tau gene mutations and neurodegeneration. Biochem Soc Symp 67:59–71

    Article  CAS  Google Scholar 

  • Goedert M, Clavaguera F, Tolnay M (2010) The propagation of prion-like protein inclusions in neurodegenerative diseases. Trends Neurosci 33(7):317–325

    Article  CAS  PubMed  Google Scholar 

  • Gong YH, Parsadanian AS, Andreeva A, Snider WD, Elliott JL (2000) Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration. J Neurosci 20(2):660–665

    CAS  PubMed  Google Scholar 

  • Group THsDCR (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72(6):971–983

    Article  Google Scholar 

  • Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng H-X, Chen W, Zhai P, Sufit RL, Siddique T (1994) Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264:1772–1775

    Article  CAS  PubMed  Google Scholar 

  • Harding AE (1981) Friedreich’s ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 104(3):589–620

    Article  CAS  PubMed  Google Scholar 

  • Hayashi H, Kato S, Kawada A (1991) Amyotrophic lateral sclerosis patients living beyond respiratory failure. J Neurol Sci 105:73–78

    Article  CAS  PubMed  Google Scholar 

  • Hely MA, Morris JG, Rail D, Reid WG, O'Sullivan DJ, Williamson PM, Genge S, Broe GA (1989) The Sydney Multicentre Study of Parkinson’s disease: a report on the first 3 years. J Neurol Neurosurg Psychiatry 52(3):324–328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirshner HS, Tanridag O, Thurman L, Whetsell WO Jr (1987) Progressive aphasia without dementia: two cases with focal spongiform degeneration. Ann Neurol 22(4):527–532

    Article  CAS  PubMed  Google Scholar 

  • Kurtland LT (1988) Amyotrophic lateral sclerosis and Parkinson's disease complex on Guam linked to an environmental neurotoxin. Trends Neurosci 11:51–54

    Article  Google Scholar 

  • Le Rhun E, Richard F, Pasquier F (2005) Natural history of primary progressive aphasia. Neurology 65(6):887–891

    Article  PubMed  Google Scholar 

  • Levy G, Tang MX, Louis ED, Cote LJ, Alfaro B, Mejia H, Stern Y, Marder K (2002) The association of incident dementia with mortality in PD. Neurology 59(11):1708–1713

    Article  CAS  PubMed  Google Scholar 

  • Lino MM, Schneider C, Caroni P (2002) Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease. J Neurosci 22(12):4825–4832

    CAS  PubMed  Google Scholar 

  • McGeer PL, McGeer EG (2002) Inflammatory processes in amyotrophic lateral sclerosis. Muscle Nerve 26(4):459–470

    Article  CAS  PubMed  Google Scholar 

  • Morgante L, Salemi G, Meneghini F, Di Rosa AE, Epifanio A, Grigoletto F, Ragonese P, Patti F, Reggio A, Di Perri R, Savettieri G (2000) Parkinson disease survival: a population-based study. Arch Neurol 57(4):507–512

    Article  CAS  PubMed  Google Scholar 

  • Nagai M, Aoki M, Miyoshi I, Kato M, Pasinelli P, Kasai N, Brown RH Jr, Itoyama Y (2001) Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease. J Neurosci 21(23):9246–9254

    CAS  PubMed  Google Scholar 

  • Oppenheimer DR, Esiri MM (1997) Diseases of the basal ganglia, cerebellum and motor neurons. In: Adams JH, Corsellis JAN, Duchen LW (eds) Greenfield’s neuropathology, 6th edn. Arnold, New York, pp 988–1045

    Google Scholar 

  • Overk CR, Masliah E (2014) Pathogenesis of synaptic degeneration in Alzheimer’s disease and Lewy body disease. Biochem Pharmacol 88(4):508–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pittman RN, Messam CA, Mills JC (1999) Asynchronous death as a characteristic feature of apoptosis. In: Koliatsos VE, Ratan RR (eds) Cell death and diseases of the nervous system. Humana Press, Totowa, NJ, pp 29–43

    Chapter  Google Scholar 

  • Pramatarova A, Laganiere J, Roussel J, Brisebois K, Rouleau GA (2001) Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J Neurosci 21(10):3369–3374

    CAS  PubMed  Google Scholar 

  • Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu W-Q, Armos KS, Cortopassi GA, Jaber L, Rotter JI, Shohat M, Fischel-Ghodsian N (1993) Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet 4:289–294

    Article  CAS  PubMed  Google Scholar 

  • Prusiner SB (1998) Prions. Proc Natl Acad Sci U S A 95(23):13363–13383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Przedborski S, Goldman JE (2004) Pathogenic role of glial cells in Parkinson’s disease. In: Hertz L (ed) Non-neuronal cells of the nervous system: function and dysfunction, vol 31, Advances in molecular and cell biology. Elsevier, New York, pp 967–982

    Chapter  Google Scholar 

  • Przedborski S, Vila M (2001) MPTP: a review of its mechanisms of neurotoxicity. Clin Neurosci Res 1(6):407–418

    Article  CAS  Google Scholar 

  • Przedborski S, Vila M, Jackson-Lewis V (2003) Neurodegeneration: what is it and where are we? J Clin Invest 111(1):3–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng H-X, Rahmani Z, Krizus A, McKenna-Yasek D, Cayabyab A, Gaston SM, Berger R, Tanzi RE, Halperin JJ, Herzfeldt B, Van den Bergh R, Hung W-Y, Bird T, Deng G, Mulder DW (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62

    Article  CAS  PubMed  Google Scholar 

  • Saper CB (1996) Any way you cut it: a new journal policy for the use of unbiased counting methods. J Comp Neurol 364(1):5

    Article  CAS  PubMed  Google Scholar 

  • Saper CB, Wainer BH, German DC (1987) Axonal and transneuronal transport in the transmission of neurological disease: potential role in system degenerations, including Alzheimer’s disease. Neuroscience 23(2):389–398

    Article  CAS  PubMed  Google Scholar 

  • Sasaki S, Tsutsumi Y, Yamane K, Sakuma H, Maruyama S (1992) Sporadic amyotrophic lateral sclerosis with extensive neurological involvement. Acta Neuropathol 84(2):211–215

    Article  CAS  PubMed  Google Scholar 

  • Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25(3):302–305

    Article  CAS  PubMed  Google Scholar 

  • Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K (2003) alpha-Synuclein locus triplication causes Parkinson’s disease. Science 302(5646):841

    Google Scholar 

  • Stacy M, Jankovic J (1992) Differentia diagnosis of Parkinson’s disease and the Parkinsonism plus syndromes. In: Cedarbaum J, Gancher S (eds) Parkinson’s disease. Neurologic clinics. W.B. Sauders Company, Philadelphia, pp 341–359

    Google Scholar 

  • Sulkava R, Haltia M, Paetau A, Wikstrom J, Palo J (1983) Accuracy of clinical diagnosis in primary degenerative dementia: correlation with neuropathological findings. J Neurol Neurosurg Psychiatry 46(1):9–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanner CM (1989) The role of environmental toxins in the etiology of Parkinson’s disease. Trends Neurosci 12:49–54

    Article  CAS  PubMed  Google Scholar 

  • Tanner CM (1992) Epidemiology of Parkinson’s disease. Neurol Clin 10(2):317–329

    CAS  PubMed  Google Scholar 

  • Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, Langston JW (1999) Parkinson disease in twins: an etiologic study. JAMA 281(4):341–346

    Article  CAS  PubMed  Google Scholar 

  • Tomlinson BE (1977) The pathology of dementia. Contemp Neurol Ser 15:113–153

    CAS  PubMed  Google Scholar 

  • Trapp BD, Nave KA (2008) Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 31:247–269

    Article  CAS  PubMed  Google Scholar 

  • Van Dijk PT, Dippel DW, Van Der Meulen JH, Habbema JD (1996) Comorbidity and its effect on mortality in nursing home patients with dementia. J Nerv Ment Dis 184(3):180–187

    Article  PubMed  Google Scholar 

  • Wenning GK, Colosimo C, Geser F, Poewe W (2004) Multiple system atrophy. Lancet Neurol 3(2):93–103

    Article  PubMed  Google Scholar 

  • West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM (2005) Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A 102(46):16842–16847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • World Health Organization (2006) Neurological disorders. Public health challenges. World Health Organization, Geneva

    Google Scholar 

  • Wyss-Coray T, Mucke L (2002) Inflammation in neurodegenerative disease-a double-edged sword. Neuron 35(3):419–432

    Article  CAS  PubMed  Google Scholar 

  • Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Muller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44(4):601–607

    Google Scholar 

  • Zlokovic BV (2010) Neurodegeneration and the neurovascular unit. Nat Med 16(12):1370–1371

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author is supported by Muscular Dystrophy Association/Wings-over-Wall Street, Target ALS, NIH/NINDS Grants (NS078614-01, NS088009-01, NS042269-08), the US Department of Defense Grant (W81WXWH-08-1-0465, SRI 5-21306, W81XWH-13-1-0416), the Parkinson’s Disease Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Serge Przedborski .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Przedborski, S. (2017). Neurodegeneration. In: Ikezu, T., Gendelman, H. (eds) Neuroimmune Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-44022-4_22

Download citation

Publish with us

Policies and ethics