Mitochondrial DNA and Inflammation in Alzheimer’s Disease

Abstract

Mitochondrial dysfunction and neuroinflammation are implicated in the pathogenesis of most neurodegenerative diseases, such as Alzheimer’s disease (AD). In fact, although a growing number of studies show crosstalk between these two processes, there remain numerous gaps in our knowledge of the mechanisms involved, which requires further clarification. On the one hand, mitochondrial dysfunction may lead to the release of mitochondrial damage-associated molecular patterns (mtDAMPs) which are recognized by microglial immune receptors and contribute to neuroinflammation progression. On the other hand, inflammatory molecules released by glial cells can influence and regulate mitochondrial function. A deeper understanding of these mechanisms may help identify biomarkers and molecular targets useful for the treatment of neurodegenerative diseases. This review of works published in recent years is focused on the description of the mitochondrial contribution to neuroinflammation and neurodegeneration, with particular attention to mitochondrial DNA (mtDNA) and AD.

Unraveling the therapeutic potential of ginsenoside compound Mc1 in Alzheimer’s disease: Exploring the role of AMPK/SIRT1/NF-κB signaling pathway and mitochondrial function

“…There is growing evidence indicating a connection between mitochondrial dysfunction and inflammatory responses in AD. 35 These dysfunctional mitochondria trigger a series of events that result in inflammation within the brain. Inflammatory responses, characterized by the release of proinflammatory mediators, exacerbate neuronal damage and contribute to the progression of AD pathophysiology.…”

Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation

“…In PD, it has been suggested that mitochondrial dysfunction can lead to the release of mitochondrial damage-associated molecular patterns (mtDAMPs), triggering neuroinflammation through microglial immune receptors. Conversely, inflammatory molecules released by the glial cells can further damage mitochondrial function, triggering a vicious circle that can lead to neurodegeneration [ 118 , 119 ]. In mental disorders such as major depression and schizophrenia, higher levels of cf-mtDNA were associated with symptoms of depression and schizophrenia.…”

The emerging role of brain neuroinflammatory responses in Alzheimer’s disease

“…Currently, Aβ42and phosphorylated tau proteins are the main fluid-based biomarkers of Cerebrospinal fluid (CSF) in clinical practice ( Bălaşa et al, 2020 ). However, there are still limitations in their specific detection based on their low concentration in blood ( Noble et al, 2014 ; Galizzi and Di Carlo, 2023 ). As mentioned, inflammation plays a major role in AD development and among all different neuroinflammatory biomarkers which can be considered as therapeutic targets for drug design, cytokines, chemokines and transcription factors for their precise roles in the various stages of AD, possible medical applications, and easy isolation from blood or CSF have attracted a lot of attention ( Zheng et al, 2016 ; AmeliMojarad et al, 2022 ; Park et al, 2022 ).…”