Genetically distinct neurodegenerative proteinopathies engage overlapping proteostasis components
- 1Department of Biotechnology, Anand School of Engineering and Technology, Sharda University Agra, Uttar Pradesh-282007, India.
Abstract
Neurodegenerative proteinopathies are defined by distinct proteins whose folding, trafficking and clearance depend on shared proteostasis machinery. Whether these disorders engage common components or only common processes has been unresolved. We mapped 16 disease proteins from 12 disorders onto a fixed 990-protein proteostasis network. Across the 12 disorders, the neighborhoods of these proteins shared specific proteins beyond expectations from process composition and connectivity. The same held for the two disorders defined by more than one protein. Nine proteins contributed disproportionately, and only autophagys removal significantly reduced similarity. Removing PRKN, HSPA8 or UBQLN2 in silico reduced path efficiency, marking them candidate shared network vulnerabilities. In human brain proteomes, Alzheimers disease-zone proteins showed greater abundance remodeling in the insoluble fraction; recurrence across disorders showed no such association. The result is a component-level architecture prioritizing network-derived candidates for cross-disease functional testing.
Related
- Large-scale forward genetics reveals genetically separable components of plant cell proliferative capacity
- Imbibitional damage and germination kinetics reveal genetically distinct components of cold sensitivity in soybean seeds
- Proteostasis in Podocytes: Role of Cargo Receptor Surf4 and Collagen IV Trafficking
- Loss of the UFM-1 pathway enhances the ER Unfolded Protein Response under stress to improve proteostasis and organismal health in Caenorhabditis elegans
- Selection signatures in Apis mellifera jemenitica suggest candidate genes potentially involved in energy metabolism, proteostasis, reproduction, and cellular regulation
BibTeX
@misc{yarlagadda2026genetically,
title = {{Genetically distinct neurodegenerative proteinopathies engage overlapping proteostasis components}},
author = {B. Yarlagadda and V. Kumar},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.753000},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.753000v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Genetically distinct neurodegenerative proteinopathies engage overlapping proteostasis components
AU - B. Yarlagadda
AU - V. Kumar
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.753000
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.753000v1
AB - Neurodegenerative proteinopathies are defined by distinct proteins whose folding, trafficking and clearance depend on shared proteostasis machinery. Whether these disorders engage common components or only common processes has been unresolved. We mapped 16 disease proteins from 12 disorders onto a fixed 990-protein proteostasis network. Across the 12 disorders, the neighborhoods of these proteins shared specific proteins beyond expectations from process composition and connectivity. The same held for the two disorders defined by more than one protein. Nine proteins contributed disproportionately, and only autophagys removal significantly reduced similarity. Removing PRKN, HSPA8 or UBQLN2 in silico reduced path efficiency, marking them candidate shared network vulnerabilities. In human brain proteomes, Alzheimers disease-zone proteins showed greater abundance remodeling in the insoluble fraction; recurrence across disorders showed no such association. The result is a component-level architecture prioritizing network-derived candidates for cross-disease functional testing.
ER -