Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases

Examples of amyloidopathies, tauopathies and synucleinopathies

Mathieu Bourdenx, Nikolaos Stavros Koulakiotis, Despina Sanoudou, Erwan Bezard, Benjamin Dehay, Anthony Tsarbopoulos

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative diseases that generate important health-related direct and indirect socio-economic costs. They are characterized by severe neuronal losses in several disease-specific brain regions associated with deposits of aggregated proteins. In Alzheimer's disease, β-amyloid peptide-containing plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated microtubule-associated protein tau are the two main neuropathological lesions, while Parkinson's disease is defined by the presence of Lewy Bodies that are intraneuronal proteinaceous cytoplasmic inclusions. α-Synuclein has been identified as a major protein component of Lewy Bodies and heavily implicated in the pathogenesis of Parkinson's disease. In the past few years, evidence has emerged to explain how these aggregate-prone proteins can undergo spontaneous self-aggregation, propagate from cell to cell, and mediate neurotoxicity. Current research now indicates that oligomeric forms are probably the toxic species. This article discusses recent progress in the understanding of the pathogenesis of these diseases, with a focus on the underlying mechanisms of protein aggregation, and emphasizes the pathophysiological molecular mechanisms leading to cellular toxicity. Finally, we present the putative direct link between β-amyloid peptide and tau in causing toxicity in Alzheimer's disease as well as α-synuclein in Parkinson's disease, along with some of the most promising therapeutic strategies currently in development for those incurable neurodegenerative disorders.

Original languageEnglish
JournalProgress in Neurobiology
DOIs
Publication statusAccepted/In press - 6 Feb 2015
Externally publishedYes

Fingerprint

Tauopathies
Neurodegenerative Diseases
Parkinson Disease
Synucleins
Lewy Bodies
Alzheimer Disease
Amyloid
Proteins
Cell Aggregation
Peptides
Neurofibrillary Tangles
Microtubule-Associated Proteins
Poisons
Inclusion Bodies
Brain Diseases
Economics
Costs and Cost Analysis
Health
Research

Keywords

  • Alzheimer's disease
  • Neurodegeneration
  • Parkinson's disease
  • Protein aggregation
  • Spreading
  • Therapeutic

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases : Examples of amyloidopathies, tauopathies and synucleinopathies. / Bourdenx, Mathieu; Koulakiotis, Nikolaos Stavros; Sanoudou, Despina; Bezard, Erwan; Dehay, Benjamin; Tsarbopoulos, Anthony.

In: Progress in Neurobiology, 06.02.2015.

Research output: Contribution to journalArticle

Bourdenx, Mathieu ; Koulakiotis, Nikolaos Stavros ; Sanoudou, Despina ; Bezard, Erwan ; Dehay, Benjamin ; Tsarbopoulos, Anthony. / Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases : Examples of amyloidopathies, tauopathies and synucleinopathies. In: Progress in Neurobiology. 2015.
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