Chaperone‐Mediated Autophagy: A Critical Regulator of Neuroinflammation and Neurodegeneration
Source abstract
Abstract
Abstract Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by hallmark pathological features such as the accumulation of misfolded proteins and neuroinflammation. Chaperone‐mediated autophagy (CMA), a selective lysosomal pathway, facilitates the degradation of proteins containing KFERQ‐like motifs via the receptor lysosome‐associated membrane protein type 2A (LAMP2A). In the recent review, the pivotal role of CMA in regulating proteostasis and modulating inflammatory responses is highlighted. This commentary explores the multifaceted roles of CMA in neurodegenerative disease progression, emphasizing its involvement in age‐related decline, feedback loops between CMA dysregulation and neurodegeneration, and potential as a therapeutic target. Emerging CMA activators and the challenges of modulating CMA for clinical use are also discussed.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Autophagy in Disease and Therapy · Endoplasmic Reticulum Stress and Disease · Calcium signaling and nucleotide metabolism
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pharmacy The Fourth Affiliated Hospital of Soochow University Suzhou Dushu Lake Hospital Medical Center of Soochow University Suzhou 215123 China
Laboratory of Molecular Neuropathology Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow University Suzhou 215123 China
Funding
National Natural Science Foundation of China · Natural Science Foundation of Jiangsu Province
References (45)
Show source-provided references
1. 10.1016/j.cellsig.2019.10944210.1016/j.cellsig.2019.109442 ↗
2. 10.1038/s41580-018-0001-610.1038/s41580-018-0001-6 ↗
3. 10.1016/j.neuron.2022.01.01710.1016/j.neuron.2022.01.017 ↗
4. 10.1126/science.279939110.1126/science.2799391 ↗
5. 10.1242/jcs.113.24.444110.1242/jcs.113.24.4441 ↗
6. 10.1016/j.mam.2021.10102510.1016/j.mam.2021.101025 ↗
7. 10.1128/MCB.02070-0710.1128/MCB.02070-07 ↗
8. 10.1371/journal.pbio.300030110.1371/journal.pbio.3000301 ↗
9. 10.1016/j.neuron.2024.05.01810.1016/j.neuron.2024.05.018 ↗
10. Palmer J. E. · Neuron · 2007 · 0896
11. 10.1242/jcs.00107310.1242/jcs.001073 ↗
12. 10.1073/pnas.232292912110.1073/pnas.2322929121 ↗
13. 10.3389/fragi.2024.150940010.3389/fragi.2024.1509400 ↗
14. 10.1111/acel.1231010.1111/acel.12310 ↗
15. 10.1080/15548627.2019.160354510.1080/15548627.2019.1603545 ↗
16. 10.1073/pnas.231794512110.1073/pnas.2317945121 ↗
17. 10.1038/ni.300310.1038/ni.3003 ↗
18. 10.1186/s13024-023-00672-x10.1186/s13024-023-00672-x ↗
19. 10.14336/AD.2023.051210.14336/AD.2023.0512 ↗
20. 10.1146/annurev-immunol-051116-05235810.1146/annurev-immunol-051116-052358 ↗
21. 10.1126/sciadv.adi834310.1126/sciadv.adi8343 ↗
22. 10.1186/s12974-021-02349-y10.1186/s12974-021-02349-y ↗
23. 10.1161/CIRCRESAHA.121.31890810.1161/CIRCRESAHA.121.318908 ↗
24. 10.3389/fimmu.2020.58904810.3389/fimmu.2020.589048 ↗
25. 10.1016/j.immuni.2016.08.01410.1016/j.immuni.2016.08.014 ↗
26. 10.1038/s41593-019-0566-110.1038/s41593-019-0566-1 ↗
27. 10.1016/S0040-8166(02)00105-210.1016/S0040-8166(02)00105-2 ↗
28. 10.1093/cercor/bhac00710.1093/cercor/bhac007 ↗
29. 10.1016/j.stemcr.2018.12.01110.1016/j.stemcr.2018.12.011 ↗
30. 10.1074/jbc.M80199220010.1074/jbc.M801992200 ↗
31. 10.1126/science.110173810.1126/science.1101738 ↗
32. Martinez‐Vicente M. · J. Clin. Invest. · 2008 · 118 · 777
33. 10.1016/j.cell.2021.03.04810.1016/j.cell.2021.03.048 ↗
34. 10.1038/s41467-021-22501-910.1038/s41467-021-22501-9 ↗
35. 10.1073/pnas.212113311910.1073/pnas.2121133119 ↗
36. 10.1038/oncsis.2017.8510.1038/oncsis.2017.85 ↗
37. 10.1038/nchembio.123010.1038/nchembio.1230 ↗
38. 10.1038/s41467-022-31869-110.1038/s41467-022-31869-1 ↗
39. 10.1007/s13238-021-00858-310.1007/s13238-021-00858-3 ↗
40. 10.1186/s40035-019-0159-710.1186/s40035-019-0159-7 ↗
41. 10.1089/ars.2013.539910.1089/ars.2013.5399 ↗
42. 10.1038/s41583-022-00588-310.1038/s41583-022-00588-3 ↗
43. 10.1038/s41580-022-00529-z10.1038/s41580-022-00529-z ↗
44. 10.1093/hmg/ddp36710.1093/hmg/ddp367 ↗
45. 10.1016/j.cmet.2014.06.00910.1016/j.cmet.2014.06.009 ↗