Protein aggregation disorders

Tiago Fleming Outeiro, Pamela J McLean, Bradley T. Hyman

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

Protein aggregation disorders are a group of diseases that arise because of or are associated with the misfolding and aggregation of one or more proteins. They are believed to result from the failure of proteins to reach their active state or from the accumulation of abnormally folded proteins. Despite the strong connection between protein misfolding and aggregation and disease, the manner by which it results in disease is still unknown. The "amyloid hypothesis" states that the aggregation of proteins into an ordered fibrillar structure is causally related to aberrant protein interactions that culminate in neuronal dysfunction and ultimately neurodegeneration. Evidence from a variety of diseases suggests that specific alterations in the primary sequence of cellular proteins, posttranslational modifications, or defective interactions with other proteins can impose conformational constraints that alter the normal function/biology of these proteins and facilitate aggregation. Protein aggregation disorders include Alzheimer's disease (AD), synucleinopathies [Parkinson's disease (PD)], and prion diseases. Accumulation of Aβ in the brain is the primary culprit of AD-related pathogenesis, including neurofibrillary tangles (NFT) formation, synapse loss, and neuronal cell death. In PD, the disconnection between pathogenesis and α-synuclein inclusion formation adds support for roles of α-synuclein oligomers in toxicity and pathogenesis. The accumulation of PrPSc (prion protein) in the brain is the hallmark of prion diseases, but, as in other neurodegenerative diseases, whether it is directly responsible for the devastating pathology is still unclear.

Original languageEnglish (US)
Title of host publicationNeurobiology of Disease
PublisherElsevier Inc.
Pages111-123
Number of pages13
ISBN (Print)9780120885923
DOIs
StatePublished - 2007
Externally publishedYes

Fingerprint

Proteins
Synucleins
Prion Diseases
Parkinson Disease
Alzheimer Disease
Proteostasis Deficiencies
PrPSc Proteins
Neurofibrillary Tangles
Brain
Post Translational Protein Processing
Amyloid
Neurodegenerative Diseases
Synapses
Cell Death
Pathology

ASJC Scopus subject areas

  • Dentistry(all)
  • Medicine(all)

Cite this

Outeiro, T. F., McLean, P. J., & Hyman, B. T. (2007). Protein aggregation disorders. In Neurobiology of Disease (pp. 111-123). Elsevier Inc.. https://doi.org/10.1016/B978-012088592-3/50012-8

Protein aggregation disorders. / Outeiro, Tiago Fleming; McLean, Pamela J; Hyman, Bradley T.

Neurobiology of Disease. Elsevier Inc., 2007. p. 111-123.

Research output: Chapter in Book/Report/Conference proceedingChapter

Outeiro, TF, McLean, PJ & Hyman, BT 2007, Protein aggregation disorders. in Neurobiology of Disease. Elsevier Inc., pp. 111-123. https://doi.org/10.1016/B978-012088592-3/50012-8
Outeiro TF, McLean PJ, Hyman BT. Protein aggregation disorders. In Neurobiology of Disease. Elsevier Inc. 2007. p. 111-123 https://doi.org/10.1016/B978-012088592-3/50012-8
Outeiro, Tiago Fleming ; McLean, Pamela J ; Hyman, Bradley T. / Protein aggregation disorders. Neurobiology of Disease. Elsevier Inc., 2007. pp. 111-123
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