Tomm40, a Risk Gene for Alzheimer’s Disease, Is Upregulated During Proinflammatory Response

Document Type

Article

Publication Date

12-31-2021

Publication Title

Alzheimer's & Dementia: The Journal of the Alzheimer's Association

Volume

17

First page number:

e058711

Abstract

BACKGROUND: TOMM40 gene has been associated with a risk of Alzheimer's disease (Brabec et al., 2021). TOMM40 codes for the protein TOM40, which is the main channel forming protein for the translocase of outer membrane (TOM) in mitochondria. TOM40 is required for the efficient pre-protein transport (Rapaport & Neupert, 1999). A large body of research has been accumulated on the involvement of mitochondria, especially TOM40 pore, in the progression of various diseases, including Alzheimer's disease (Ahmad, 2019, Gottschalk et al., 2014). Furthermore, TOMM40 is found to be downregulated in brain and blood of patients with Alzheimer's disease (Lee et al., 2012). As this gene is being explored with increased interest, its mechanisms in microglial responses have not yet been examined directly. In our study, we are attempting to elucidate the role of TOMM40 during microglial pro-inflammatory responses in a murine and human microglial cell line. METHOD: An immortalized murine microglial cell line BV-2 and human HMC3 cells were used in this study. Microglial inflammation was triggered with proinflammatory agent, lipopolysaccharide (LPS), 10 ng/ml, 100 ng/ml, for 24 hours. During the stimulation, microglial morphology was monitored with phase-contrast microscope, and TOMM40 gene expression wer measured along with proinflammatory genes (TNF-α and NLRP3) by Quantitative Real-Time PCR (qRT-PCR). In addition, we also used Western blot to check the TOM40 protein expression. RESULT: We found that microglia cells were more amoeboid shape with LPS treatment, as compared to original ramified microglia without LPS treatment. qRT-PCR results showed that TOMM40, TNF-α, and NLRP3 RNA expression were all upregulated in HMC3 cells when treated with LPS. TOM40 protein was also increased in BV2 cells with Western blot. CONCLUSION: Our preliminary data showed that TOMM40 gene expression was upregulated in microglia cells during proinflammatory response, which was consistent with previous findings from Alzheimer's disease. Our data highlights that we can use the microglial cell lines to study the role of TOMM40 in the progress of Alzheimer's disease. The project is an undergoing study. Further function and pathway studies in the line will help to design new drugs for Alzheimer's disease prevention and treatment.

Controlled Subject

Alzheimer's disease; Sexual minorities

Disciplines

Immunology and Infectious Disease | Molecular, Genetic, and Biochemical Nutrition | Nervous System

UNLV article access

Search your library

Share

COinS