TFEB [Neurosurgery Wiki]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.
====== TFEB ======

[[Atmospheric particulate matter]] (PM) exacerbates the risk factor for Alzheimer's and [[Parkinson's disease]]s (PD) by promoting the [[alpha-synuclein]] (α-syn) pathology in the brain. However, the molecular mechanisms of astrocytes involvement in α-syn pathology underlying the process remain unclear. 

Li et al.in a study investigated PM with particle size <200 nm (PM0.2) exposure-induced α-syn pathology in ICR mice and primary astrocytes, then assessed the effects of mammalian target of rapamycin inhibitor (PP242) in vitro studies. We observed the α-syn pathology in the brains of exposed mice. Meanwhile, PM0.2-exposed mice also exhibited the activation of glial cell and the inhibition of autophagy. In vitro study, PM0.2 (3, 10 and 30 µg/mL) induced inflammatory response and the disorders of α-syn degradation in primary astrocytes, and lysosomal-associated membrane protein 2 (LAMP2)-mediated autophagy underlies α-syn pathology. The abnormal function of autophagy-lysosome was specifically manifested as the expression of microtubule-associated protein light chain 3 (LC3II), cathepsin B (CTSB) and lysosomal abundance increased first and then decreased, which might both be a compensatory mechanism to toxic α-syn accumulation induced by PM0.2. Moreover, with the transcription factor EB (TFEB) subcellular localization and the increase in LC3II, LAMP2, CTSB, and cathepsin D proteins were identified, leading to the restoration of the degradation of α-syn after the intervention of PP242. Our results identified that PM0.2 exposure could promote the α-syn pathological dysregulation in [[astrocyte]]s, providing mechanistic insights into how PM0.2 increases the risk of developing PD and highlighting TFEB/[[LAMP2]] as a promising therapeutic target for antagonizing PM0.2 toxicity
((Li B, Liu T, Shen Y, Qin J, Chang X, Wu M, Guo J, Liu L, Wei C, Lyu Y, Tian F, Yin J, Wang T, Zhang W, Qiu Y. [[TFEB]]/[[LAMP2]] contributes to PM0.2-induced autophagy-lysosome dysfunction and alpha-synuclein dysregulation in astrocytes. J Environ Sci (China). 2024 Nov;145:117-127. doi: 10.1016/j.jes.2023.09.036. Epub 2023 Oct 5. PMID: 38844312.)).