Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.
Level 5 - mechanism / opinion, no new human data
Narrative review of biological mechanisms and therapeutic strategies without systematic review methodology or new human data.
PubMed 42450002 · doi:10.3390/ijms27135730
What was done
This narrative review synthesized literature on ubiquitin-proteasome system (UPS) dysfunction across major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. The authors examined mechanisms of proteasome impairment by disease-associated proteins, the contributions of aging, oxidative stress, and neuroinflammation, and evaluated emerging therapeutic strategies such as pharmacological activation and targeted protein degradation.
What was found
The abstract reports no numerical findings or quantitative metrics. It qualitatively summarizes that proteasome dysfunction occurs via direct inhibition, defective substrate processing, and sequestration into aggregates, with mechanisms varying across disease contexts.
Why it matters
It provides a synthesized overview of proteostasis failure across multiple neurodegenerative diseases and outlines therapeutic concepts aimed at restoring proteasomal clearance.
Limits
The paper is a non-systematic narrative review providing no primary experimental data, quantitative synthesis, or human clinical trial results. Clinical feasibility and therapeutic efficacy of the discussed approaches remain unproven in the abstract.
Cited by
- supports Virtually all neurodegenerative diseases feature the aggregation of abnormal protein clumps either inside neurons or in the extracellular spaces between neurons.