Proteopathies (Proteinopathies)

  • Richard Dods


In this chapter, we review the diseases caused by misfolding of proteins. The more common proteopathies such as Alzheimer’s disease, Parkinson’s disease, Huntington disease, amyotrophic lateral sclerosis, human prion disease, and muscle dystrophy (and its many forms) are described. Deposits of amyloidosis and tau, which deposit in many proteopathies are characterized and their functions are described.



Alzheimer’s disease

is caused by misfolded β-amyloid proteins. It is one of the most common proteopathies.


is a hormone which is packaged with insulin and secreted from the beta cells in the pancreas.


is a condition in which deposits of amyloid are found in various organs.

Amyotrophic lateral sclerosis (ALS)

is a neurodegenerative disease caused by mutations that lead to misfolding of copper-zinc superoxide dismutase 1.

Becker muscular dystrophy

is caused by mutations in the dystrophin gene.

Congenital muscular dystrophy

is caused by mutations in laminin-α2.

Congo red dye

complexes with amyloid to form a substance that exhibits a green birefringence when exposed to polarized light.

Distal muscular dystrophy

is caused by mutations in the dysferlin gene.

Duchenne muscular dystrophy

is caused by a mutation of the dystrophin gene. It is the most common form of muscular dystrophy.

Emery–Dreyfus muscular dystrophy

is caused by mutations in the lamin A/C gene, and emerin gene, syne1 and 2.

Facioscapulohumeral muscular dystrophy

is caused by mutations in the double homeobox 4 gene.

FAD (familial Alzheimer’s disease)

is a rare form of Alzheimer’s disease.


is a geometrical shape formed by an amyloid deposit.


is a comorbid condition to ALS. Comorbid means that the condition occurs with another disease.


is a protein which when misfolded has symptoms similar to those of ALS especially in that it progresses more slowly than does ALS.

Human prion diseases

are neurodegenerative diseases that are inheritable and are transmitted by misfolded proteins.

Huntington’s disease

refers to a neurodegenerative disease caused by misfolding of huntingtin protein.

Lewy bodies

are cytoplasmic inclusions.

Limb-girdle muscular dystrophy

is the name given to a long list of disorders that is enumerated in the text.

Misfolding of Synuclein

is the cause of Parkinson’s disease (both familial and sporadic).

Myotonic muscular dystrophy (Steinert’s disease)

is a common form of muscular dystrophy.

Myotonic muscular dystrophy type 1

is a form of muscular dystrophy caused by expansion of the repeat region of the dystrophia myotonica protein kinase.

Myotonic muscular dystrophy type 2

is caused by a mutation in nucleic acid-binding protein.

Oculopharyngeal muscular dystrophy

is caused by mutations in the polyadenylate binding protein nuclear 1.

Parkinson’s disease

is the second most common neurodegenerative condition of greater than 65 years of age.

SAD (sporadic Alzheimer’s disease)

is the common form of Alzheimer’s disease.

Steric Zipper

is a geometrical shape taken when amino acid side chains of a β-sheet interdigitates with the side chains of amino acids of an adjacent β-sheet (similar to the teeth of a zipper).


are a group of neurodegenerative diseases characterized by fibrillary aggregates of α-synuclein. Misfolding of synuclein is currently believed to be one of the causes of Parkinson’s disease.


is a DNA binding protein which when misfolded by mutation is a cause of Alzheimer’s disease.


is an intrinsically disordered phosphoprotein used for the formation of microtubules.

Tau phosphorylation

is exhibited in several proteopathies.


is a neurogenerative disease caused by mutated ubiquilin.

Further Reading

  1. Guo P, Lam SL (2016) Unusual structures of CCTG repeats and their participation in repeat expansion. Bio Mol Concepts: 7(5-6):331. Doi: Scholar
  2. Zhou L, Lu HL. Targeting fibrosis in Duchenne muscular dystrophy. J Neuropath Exp Neurol: 69:771. Doi: Scholar
  3. Holmberg J, Durbeej M. (2013) Laminin-211 in skeletal muscle function. Cell Adhesion Migration:7:111.CrossRefGoogle Scholar
  4. Reinhard JR, Lin S, McKee KK, et al. (2017). Linker proteins basement membrane and correct LAMA2-related muscular dystrophy in mice. Sci Transl Med:9:eaal4649. Doi: Scholar
  5. Lemmers RJL, van der Vliet PJ, Klooster R, et al. (2010). A unifying genetic model for fascioscapulohumeral muscular dystrophy. Science:329:1650. Doi: Scholar
  6. Brais B, Bouchard J-P, Xie Y-G, et al. (1998). Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nat Genet: 18:164.CrossRefGoogle Scholar
  7. Abu-Baker A, Messaed C, Laganiere J, et al. (2003) Involvement of the ubiquitin-proteosome pathway and molecular chaperones in oculopharyngeal muscular dystrophy. Hum Mol Genet: 12:2609. Doi: Scholar
  8. Calado A, Tomé FMS, Brais B, et al. (2000) Nuclear inclusions in oculopharyngeal muscular dystrophy consist of poly(A) binding protein 2 aggregates which sequester poly(A) RNA. Hum Mol Genet:9:2321.CrossRefGoogle Scholar
  9. Miyoshi K, Kawai H, Iwasa M, et al.(1986) Autosomal recessive distal muscular dystrophy as a new type of progressive muscular dystrophy: seventeen cases in eight families including an autopsied case. Brain:109:31. Doi: Scholar
  10. Hackman P, Vihola A, Haravuori H, et al.(2002) Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein Titin. Am J Hum Genet:71:492.CrossRefGoogle Scholar
  11. Nishino I, Carrillo-Carrasco N, Argove Z. (2013) GNE myopathy: current update and future therapy. J Neurol Neurosurg Psychiatry: 86:385. Scholar
  12. Udd B. (2014) Distal myopathies. Curr Neurol Neurosci Rep 14:434. Scholar
  13. Dittmer T, Misteli T. (2011). The lamin protein family. Genome Biol: 12:222.CrossRefGoogle Scholar
  14. Concha-Marambio L, Pritzkow S., Moda F, et al. (2016). Detection of prions in blood from patients with vatiant Creutzfeldt-Jakob disease. Sci Transl Med:8:370ra183.CrossRefGoogle Scholar
  15. Bougard D, Brandel J-P, Bélondrade M, et al. (2016) Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease. Sci Transl Med:8:370ra182.CrossRefGoogle Scholar
  16. Imran M, Mahmood S. (2011) An overview of human prion diseases. Virol J:8:559.CrossRefGoogle Scholar
  17. Bernardi L, Cupidi C, Bruni AC. (2017) Pathogenic mechanisms of the prion protein gene mutations: a review and speculative hypotheses for pathogenic potential of the Pro39Leu mutation in the associated FTD-like phenotype. J Neurol Neurosci: 8:208. doi: Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Richard Dods
    • 1
  1. 1.Illinois Mathematics and Science AcademyPalatineUSA

Personalised recommendations