Proteostasis imbalance: Unraveling protein aggregation in neurodegenerative diseases and emerging therapeutic strategies.
Level 5 - mechanism / opinion, no new human data
Narrative review describing biological mechanisms without original human data
PubMed 40610071 · doi:10.1016/bs.apcsb.2024.11.008
What was done
This chapter/review synthesizes cellular proteostasis mechanisms (molecular chaperones, the ubiquitin-proteasome system, autophagy-lysosomal pathways, and mitochondrial quality control) involved in neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. It surveys emerging therapeutic approaches aimed at restoring protein folding, degradation, and clearance.
What was found
The abstract provides a qualitative overview of disease mechanisms and therapeutic classes (small-molecule chaperones, gene therapy, RNA-based therapies, immunotherapy, autophagy inducers, and stem cells). No empirical data, quantitative findings, or specific clinical trial metrics are reported in the abstract.
Why it matters
It organizes the mechanistic links between proteostasis failure and neurodegenerative proteinopathies, summarizing diverse translational strategies intended to halt or slow disease progression.
Limits
As a narrative review, it presents conceptual and mechanistic overviews rather than systematic literature synthesis or primary empirical data. Significant translational barriers highlighted by the authors include limited blood-brain barrier penetration, off-target side effects, and insufficient target selectivity.
Cited by
- supports Most neurodegenerative diseases are caused by the accumulation of toxic protein aggregates resulting from either excessive unfolded protein production or deficiencies in autophagic and lysosomal machineries.