Abstract
Alzheimer's disease (AD) is the leading cause of dementia, affecting approximately 45.0 million people worldwide and ranking as the fifth leading cause of mortality. AD is identified by neurofibrillary tangles (NFTs), which include abnormally phosphorylated tau-protein and amyloid protein (amyloid plaques). Peptide dysregulation is caused by an imbalance between the production and clearance of the amyloid-beta (Aβ) and NFT. AD begins to develop when these peptides are not cleared from the body. As a result, understanding the processes that control both normal and pathological protein recycling in neuronal cells is critical. Insufficient Aβ and NFT clearance are important factors in the development of AD. Autophagy, lysosomal dysfunction, and ubiquitin-proteasome dysfunction have potential roles in the pathogenesis of many neurodegenerative disorders, particularly in AD. Modulation of these pathways may provide a novel treatment strategy for AD. Non-coding RNAs (ncRNAs) have recently emerged as important biological regulators, with particular relevance to the emergence and development of neurodegenerative disorders such as AD. ncRNAs can be used as potential therapeutic targets and diagnostic biomarkers due to their critical regulatory functions in several biological processes involved in disease development, such as the aggregation and accumulation of Aβ and NFT. It is evident that ncRNAs play a role in the pathophysiology of AD. In this communication, we explored the link between ncRNAs and AD and their regulatory mechanisms that may help in finding new therapeutic targets and AD medications.
Graphical Abstract
[http://dx.doi.org/10.3390/brainsci8090177] [PMID: 30223579]
[http://dx.doi.org/10.1002/alz.13016] [PMID: 36918389]
[http://dx.doi.org/10.1042/NS20220086] [PMID: 36687366]
[http://dx.doi.org/10.3390/ijms232112841] [PMID: 36361631]
[http://dx.doi.org/10.3390/diseases11010030] [PMID: 36810544]
[http://dx.doi.org/10.1007/s11010-021-04334-8] [PMID: 35083609]
[http://dx.doi.org/10.3389/fragi.2022.927630] [PMID: 35958270]
[http://dx.doi.org/10.1038/ncomms6659] [PMID: 25482515]
[http://dx.doi.org/10.1038/nrd.2018.109] [PMID: 30116051]
[http://dx.doi.org/10.1038/s41580-019-0101-y] [PMID: 30733602]
[http://dx.doi.org/10.1007/s12041-017-0747-1] [PMID: 28360406]
[http://dx.doi.org/10.3389/fgene.2019.00153] [PMID: 30881384]
[http://dx.doi.org/10.4103/1673-5374.244784] [PMID: 30531004]
[http://dx.doi.org/10.1002/wrna.1463] [PMID: 29327503]
[http://dx.doi.org/10.1038/s41580-020-00315-9] [PMID: 33353982]
[http://dx.doi.org/10.1007/978-3-319-42059-2_1] [PMID: 27573892]
[http://dx.doi.org/10.1155/2016/5365209] [PMID: 27881904]
[http://dx.doi.org/10.1016/j.febslet.2004.03.117] [PMID: 15165889]
[http://dx.doi.org/10.1016/B978-0-12-801105-8.00007-2] [PMID: 25172475]
[http://dx.doi.org/10.1186/s12929-020-00636-z] [PMID: 32264890]
[http://dx.doi.org/10.1126/science.1067122] [PMID: 12065827]
[http://dx.doi.org/10.1016/j.devcel.2015.02.002] [PMID: 25710535]
[http://dx.doi.org/10.2174/1567205016666190503152555] [PMID: 31456515]
[http://dx.doi.org/10.1146/annurev-neuro-061010-113613] [PMID: 21456963]
[http://dx.doi.org/10.3934/Neuroscience.2019.4.273] [PMID: 32341983]
[http://dx.doi.org/10.1155/2012/731526] [PMID: 22690349]
[http://dx.doi.org/10.1016/j.neuint.2010.12.023] [PMID: 21215781]
[http://dx.doi.org/10.1016/S0165-0173(00)00019-9] [PMID: 10967355]
[http://dx.doi.org/10.1073/pnas.1504081112] [PMID: 26034266]
[http://dx.doi.org/10.1016/j.brainres.2007.05.050] [PMID: 17586478]
[http://dx.doi.org/10.2174/156802607779318262] [PMID: 17266599]
[http://dx.doi.org/10.1007/s00702-021-02431-y] [PMID: 34689261]
[http://dx.doi.org/10.1101/cshperspect.a033951] [PMID: 30833457]
[http://dx.doi.org/10.1186/alzrt243] [PMID: 25031631]
[http://dx.doi.org/10.1016/j.cell.2006.04.014] [PMID: 16678092]
[http://dx.doi.org/10.3389/fnins.2018.00821] [PMID: 30483047]
[http://dx.doi.org/10.1007/s12264-008-0183-6] [PMID: 18500392]
[http://dx.doi.org/10.1038/sj.cdd.4401740] [PMID: 16094390]
[http://dx.doi.org/10.1038/nature02263] [PMID: 14685250]
[http://dx.doi.org/10.1016/j.biocel.2020.105746] [PMID: 32315770]
[http://dx.doi.org/10.1038/nm1066] [PMID: 15272267]
[http://dx.doi.org/10.1007/s12035-017-0820-z] [PMID: 29134514]
[http://dx.doi.org/10.1242/dmm.009761] [PMID: 22996644]
[http://dx.doi.org/10.1111/obr.13430] [PMID: 35119166]
[http://dx.doi.org/10.1073/pnas.0503689102] [PMID: 16174740]
[http://dx.doi.org/10.1074/jbc.M112.366336] [PMID: 22733824]
[http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID: 19167326]
[http://dx.doi.org/10.1126/scitranslmed.3009093] [PMID: 24990881]
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.08.003] [PMID: 24064186]
[http://dx.doi.org/10.1186/1750-1326-3-10] [PMID: 18684319]
[http://dx.doi.org/10.3390/ijms23147789] [PMID: 35887134]
[http://dx.doi.org/10.1186/s13024-016-0121-4] [PMID: 27456084]
[http://dx.doi.org/10.1038/cddis.2017.464] [PMID: 28981093]
[http://dx.doi.org/10.1155/2020/8881687] [PMID: 33029125]
[http://dx.doi.org/10.1016/j.arr.2019.01.001] [PMID: 30610928]
[http://dx.doi.org/10.1002/cpt.355] [PMID: 26910520]
[http://dx.doi.org/10.1016/j.nbd.2010.09.019] [PMID: 20888417]
[http://dx.doi.org/10.3389/fnagi.2021.709568] [PMID: 34621163]
[http://dx.doi.org/10.3389/fnmol.2021.685143] [PMID: 34421536]
[http://dx.doi.org/10.3389/fncel.2020.00028] [PMID: 32140098]
[http://dx.doi.org/10.3233/JAD-190634] [PMID: 31640099]
[http://dx.doi.org/10.1080/01616412.2018.1548747] [PMID: 31014193]
[http://dx.doi.org/10.1155/2013/601587] [PMID: 23533695]
[http://dx.doi.org/10.1016/j.neuroscience.2020.10.028] [PMID: 33197504]
[http://dx.doi.org/10.1186/gb-2010-11-5-r56] [PMID: 20507594]
[http://dx.doi.org/10.1038/nature11928] [PMID: 23446348]
[http://dx.doi.org/10.3389/fnmol.2016.00025] [PMID: 27147959]
[http://dx.doi.org/10.1186/s13024-018-0285-1] [PMID: 30314521]
[http://dx.doi.org/10.15252/embj.201387576] [PMID: 25001178]
[http://dx.doi.org/10.1093/hmg/ddv377] [PMID: 26362250]