Language
English
Publication Date
2-8-2023
Journal
International Journal of Molecular Sciences
DOI
10.3390/ijms24043380
PMID
36834792
PMCID
PMC9966039
PubMedCentral® Posted Date
2-8-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Cellular deposition of protein aggregates, one of the hallmarks of neurodegeneration, disrupts cellular functions and leads to neuronal death. Mutations, posttranslational modifications, and truncations are common molecular underpinnings in the formation of aberrant protein conformations that seed aggregation. The major proteins involved in neurodegeneration include amyloid beta (Aβ) and tau in Alzheimer's disease, α-synuclein in Parkinson's disease, and TAR DNA-binding protein (TDP-43) in amyotrophic lateral sclerosis (ALS). These proteins are described as intrinsically disordered and possess enhanced ability to partition into biomolecular condensates. In this review, we discuss the role of protein misfolding and aggregation in neurodegenerative diseases, specifically highlighting implications of changes to the primary/secondary (mutations, posttranslational modifications, and truncations) and the quaternary/supramolecular (oligomerization and condensation) structural landscapes for the four aforementioned proteins. Understanding these aggregation mechanisms provides insights into neurodegenerative diseases and their common underlying molecular pathology.
Keywords
Humans, Alzheimer Disease, Amyloid beta-Peptides, Amyotrophic Lateral Sclerosis, Neurodegenerative Diseases, Parkinson Disease, tau Proteins, Intrinsically Disordered Proteins, neurodegenerative diseases, intrinsically disordered proteins, Aβ, tau, α-synuclein, TDP-43, AlphaFold, biomolecular condensates, liquid–liquid phase separation, LLPS
Published Open-Access
yes
Recommended Citation
Tsoi, Phoebe S; Quan, My Diem; Ferreon, Josephine C; et al., "Aggregation of Disordered Proteins Associated with Neurodegeneration" (2023). Faculty, Staff and Students Publications. 8346.
https://digitalcommons.library.tmc.edu/baylor_docs/8346