% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Zahra:282332,
author = {Zahra, Fatima Tu and Kayani, Hooreen and Noreen, Samra and
Noor, Aneeqa and Zafar, Saima},
title = {{S}ynuclein {P}roteoforms: {R}ole in {H}ealth and
{D}isease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
issn = {0893-7648},
address = {Totowa, NJ},
publisher = {Humana Press},
reportid = {DZNE-2025-01293},
pages = {87},
year = {2025},
abstract = {Synucleins α, β, and γ are inherently disordered
proteins that play essential roles in neuronal physiology
and are increasingly recognized as key players in
neurodegenerative disease mechanisms. The molecular basis of
synucleinopathies, including Parkinson's disease, dementia
with Lewy bodies, and multiple system atrophy, is the
pathological aggregation and misfolding of synucleins.
However, the biological significance of the diverse
synuclein proteoforms that result from alternative splicing,
extensive post-translational modifications, and
conformational heterogeneity is still not fully understood.
This review systematically incorporates current knowledge of
the structural and functional diversity of synuclein
proteoforms, highlighting their molecular interactions and
aggregation pathways. We investigate the regulatory effects
of β and γ-synucleins (β-syn and γ-syn), which have
different physiological functions and clinical applications
in addition to influencing α-synuclein (α-syn)
aggregation. In addition to synucleins' involvement in the
central nervous system, recent findings show their role in
immune regulation and functions in peripheral tissues,
highlighting their systemic relevance. Controversial
aspects, such as the mechanisms of prion-like propagation,
proteoform-specific toxicity, and differential cellular
vulnerability, are thoroughly analyzed. Synuclein
proteoforms have been thoroughly characterized due to
developments in molecular imaging and proteomic techniques,
opening the door for targeted treatment approaches.
Developing novel treatments for mitigating the progression
of synucleinopathies and enhancing patient outcomes requires
an understanding of the complex biology of synuclein
proteoforms. The goal of this study is to present a thorough
framework that connects translational research and molecular
neurobiology in disorders related to synuclein.},
subtyp = {Review Article},
keywords = {Humans / Animals / Synucleins: metabolism / Synucleins:
chemistry / Health / Synucleinopathies: metabolism /
alpha-Synuclein: metabolism / Neurodegenerative Diseases:
metabolism / Protein Isoforms: metabolism / PTMs (Other) /
Protein misfolding (Other) / Proteoforms (Other) / Synuclein
(Other) / Synucleinopathies (Other) / Synucleins (NLM
Chemicals) / alpha-Synuclein (NLM Chemicals) / Protein
Isoforms (NLM Chemicals)},
cin = {AG Zerr},
ddc = {570},
cid = {I:(DE-2719)1440011-1},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41258277},
doi = {10.1007/s12035-025-05359-6},
url = {https://pub.dzne.de/record/282332},
}