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Factors Affecting Pathological Amyloid Protein Transformation: From Post-Translational Modifications to Chaperones
Vladimir I Muronets1,2,3, Sofiya S Kudryavtseva4, Lidia P Kurochkina4
1Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia. vimuronets@belozersky.msu.ru.
Biochemistry. Biokhimiia
|March 31, 2025
Summary
This review explores factors influencing protein misfolding in neurodegenerative diseases like Alzheimer's and Parkinson's. It highlights the role of post-translational modifications, chaperones, and gut microbiota in amyloid formation and prion diseases.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Neurodegenerative diseases such as Alzheimer's and Parkinson's are characterized by the pathological transformation of amyloidogenic proteins.
- Key proteins involved include alpha-synuclein, prion protein, and beta-amyloid peptide.
- Understanding the factors influencing this transformation is crucial for disease mechanism elucidation.
Purpose of the Study:
- To review the influence of various factors on the pathological transformation of amyloidogenic proteins.
- To focus on the roles of post-translational modifications, chaperones, and gastrointestinal microbiota.
- To discuss the implications for neurodegenerative diseases and spongiform encephalopathies.
Main Methods:
- Literature review of studies on protein misfolding and aggregation.
- Analysis of factors including post-translational modifications (glycation, S-nitrosylation), chemical compounds (cinnamic acid derivatives, dendrimers), and molecular chaperones.
- Examination of the role of gastrointestinal microbiota in prion pathogenesis.
Main Results:
- Post-translational modifications and chaperones significantly impact the pathological transformation of amyloidogenic proteins.
- Specific factors like glycation, S-nitrosylation, cinnamic acid derivatives, dendrimers, and various chaperonins modulate protein behavior.
- Gastrointestinal microbiota plays a notable role in the pathogenesis of amyloid neurodegenerative diseases, particularly in infectious prion transformation.
Conclusions:
- Multiple factors, including molecular and microbial elements, contribute to the development of amyloidogenic diseases.
- Targeting these factors, such as modulating gut microbiota or understanding chaperone interactions, may offer therapeutic avenues.
- Further research into the interplay between host factors and protein pathology is warranted for Alzheimer's, Parkinson's, and prion diseases.
