The Role of Microglia with Mitochondrial Dysfunction and Its Therapeutic Prospects in Alzheimer's Disease

² Shenzhen Key Laboratory of Drug Addiction, Shenzhen Neher Neural Plasticity Laboratory, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, Guangdong, China

^*Correspondence: yl.xu1@siat.ac.cn (Yunlong Xu); zxh419@163.com (Xuehui Zeng); fuxiang2004@126.com (Fuxiang Zheng)

J. Integr. Neurosci. 2024, 23(5), 91; https://doi.org/10.31083/j.jin2305091

Submitted: 27 November 2023 | Revised: 28 January 2024 | Accepted: 26 February 2024 | Published: 30 April 2024

This is an open access article under the CC BY 4.0 license.

Abstract

Alzheimer’s disease (AD), a primary cause of dementia, is rapidly emerging as one of the most financially taxing, lethal, and burdensome diseases of the 21st century. Increasing evidence suggests that microglia-mediated neuroinflammation plays a key role in both the initiation and progression of AD. Recently, emerging evidence has demonstrated mitochondrial dysfunction, particular in microglia where precedes neuroinflammation in AD. Multiple signaling pathways are implicated in this process and pharmaceutical interventions are potentially involved in AD treatment. In this review, advance over the last five years in the signaling pathways and pharmaceutical interventions are summarized and it is proposed that targeting the signaling pathways in microglia with mitochondrial dysfunction could represent a novel direction for AD treatment.

Keywords

Alzheimer's disease

microglia

mitochondria

microglia with mitochondrial dysfunction

Funding

JCYJ20210324111213037/Shenzhen Science and Technology Program

2023M733658/China Postdoctoral Science Foundation

Figures

Fig. 1.

Previous article in this issue

Next article in this issue

Fig. 1.

Mitochondrial dysfunction in microglia associated with Alzheimer’s disease. Mitochondria perform multiple roles, including energy metabolism, mitochondrial dynamics, mitochondrial biogenesis, and mitochondrial autophagy. Each function participates in various signaling pathways. Microglia with mitochondrial dysfunction significantly contribute to neuroinflammation in Alzheimer’s disease. Figure was made by biorender (https://www.biorender.com/). ROS, reactive oxygen species; ATP, denosine triphosphate; Acetyl-CoA, acetyl coenzyme A; TCA, tricarboxylic acid cycle; $\alpha{}$ -KG, $\alpha{}$ -ketoglutarate; CytC, Cytochrome C; ADP, Adenosine diphosphate; Mfn1, mitofusin-1; Mfn2, mitofusin-2; Opa1, Optic atrophy 1; Drp-1, dynamin related protein 1; Fis-1, mitochondrial fission 1 protein; PGC-1 $\alpha{}$ , peroxisome proliferator-activated receptor gamma coactivator 1 alpha; TF, Transcription factor; Nrf1/2, Nuclear respiratory factor 1/2; Nfe, nuclear factor ets-like; TFAM, mitochondrial transcription factor A; mtDNA, mitochondrial DNA; PINK, PTEN-induced kinase 1; PTEN, Phosphatase and tensin homolog; BNIP3, BCL2/adenovirus E1B interacting protein 3; BCL2, B-cell lymphoma 2; FUNDC1, FUN14 domain containing 1; AD, Alzheimer’s disease; NADH, Nicotinamide adenine dinucleotide; NIX, NIP3-like protein X.

1 of 2

J. Integr. Neurosci. Print ISSN 0219-6352 Electronic ISSN 1757-448X