Work

TMEM106B knockdown exhibits a neuroprotective effect in Parkinson's disease models via regulating autophagy-lysosome pathway

Year: 2024

Type: article

Abstract: TMEM106B, a lysosomal transmembrane protein, has been reported to be associated with Parkinson's disease (PD). However, the precise physiopathologic mechanism of TMEM106B in PD remains unclear. This study aimed to explore the influence of TMEM106B on the autophagy-lysosome pathway (ALP) in PD. 55 patients with PD and 40 healthy controls were enrolled. RT-qPCR and ELISA were employed to assess the levels of TMEM106B. In vitro and in vivo models of PD, Lentivirus-shTMEM106B and AAV-shTMEM106B were used to knockdown the expression of TMEM106B. Behavioral experiments, western blot, immunofluorescence, and immunohistochemistry were used to detect the effect of TMEM106B on the ALP process. We found that the levels of TMEM106B were increased in the PD patients and PD models. TMEM106B knockdown markedly improved the motor deficits and tyrosine hydroxylase (TH) expression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice. TMEM106B knockdown promoted α-syn clearance by regulating the ALP process in MPP + -induced SH-SY5Y cells and MPTP-treated mice. Further studies revealed that TMEM106B knockdown might activate ALP through activating AMPK-mTOR-TFEB axis. Furthermore, TMEM106B may play a vital role in the ALP by mediating the expression of TDP43. Conclusions : Taken together, our study suggests that TMEM106B knockdown mediates the ALP pathway, leading to a decrease in α-syn, providing a new direction and perspective for the regulation of autophagy in PD. • TMEM106B was increased in PD patients and PD models. • TMEM106B knockdown increased TDP43 expression in PD models. • TMEM106B knockdown attenuated the aggregation of α-syn through regulating ALP and apoptosis in PD models. • TMEM106B knockdown alleviated the loss of DA neurons and motor impairment of PD mice treated with MPTP.

Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI: 10.1016/j.bbadis.2024.167553

Authors: Yumei Liu, Kunpeng Qin, Kaixin Dou, Jiwen Ren, Binghui Hou, Anmu Xie

Institution: Affiliated Hospital of Qingdao University

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,810