The contribution of mitochondria-associated endoplasmic reticulum membranes (MAMs) dysfunction in Alzheimer’s disease and the potential countermeasure

Li, Zehui; Cao, Yu; Hui, Pei; Ma, Lei; Yang, Yang; Li, Hao

doi:10.3389/fnins.2023.1158204

Cited by 9 publications

(7 citation statements)

References 68 publications

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“…Organelles, including mitochondria and endoplasmic reticulum, have long been implicated in AD pathogenesis. 30 , 31 Gene ontology meta-analysis of top-ranked aggregate proteins (as predicted by NN analysis of network structure) revealed that ∼20% of them are mitochondrial. This suggests two possibilities: ( i . )…”

Section: Discussionmentioning

confidence: 99%

Alzheimer’s-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets

Balasubramaniam,

Ganne,

Mainali

et al. 2024

iScience

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Section: Discussionmentioning

confidence: 99%

Alzheimer’s-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets

Balasubramaniam,

Ganne,

Mainali

et al. 2024

iScience

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“…Schon's laboratory also reported that two important subunits of the catalytic presenilin subunit of γ-secretase, presenilin-1 (PS1) and presenilin-2 (PS2), are highly enriched in MAMs (Area-Gomez et al, 2009 ). MAMs also exhibit lipid raft characteristics, thus providing a favorable environment in which γ-secretase activity can target APP (Li et al, 2023b ). Important enzymes involved in APP processing, such as β- and γ-secretases, are located within lipid rafts.…”

Section: How Aβ Accumulates In Mitochondriamentioning

confidence: 99%

Neurotoxic β-amyloid oligomers cause mitochondrial dysfunction—the trigger for PANoptosis in neurons

Meng,

Song,

Liu

et al. 2024

Front. Aging Neurosci.

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As the global population ages, the incidence of elderly patients with dementia, represented by Alzheimer's disease (AD), will continue to increase. Previous studies have suggested that β-amyloid protein (Aβ) deposition is a key factor leading to AD. However, the clinical efficacy of treating AD with anti-Aβ protein antibodies is not satisfactory, suggesting that Aβ amyloidosis may be a pathological change rather than a key factor leading to AD. Identification of the causes of AD and development of corresponding prevention and treatment strategies is an important goal of current research. Following the discovery of soluble oligomeric forms of Aβ (AβO) in 1998, scientists began to focus on the neurotoxicity of AβOs. As an endogenous neurotoxin, the active growth of AβOs can lead to neuronal death, which is believed to occur before plaque formation, suggesting that AβOs are the key factors leading to AD. PANoptosis, a newly proposed concept of cell death that includes known modes of pyroptosis, apoptosis, and necroptosis, is a form of cell death regulated by the PANoptosome complex. Neuronal survival depends on proper mitochondrial function. Under conditions of AβO interference, mitochondrial dysfunction occurs, releasing lethal contents as potential upstream effectors of the PANoptosome. Considering the critical role of neurons in cognitive function and the development of AD as well as the regulatory role of mitochondrial function in neuronal survival, investigation of the potential mechanisms leading to neuronal PANoptosis is crucial. This review describes the disruption of neuronal mitochondrial function by AβOs and elucidates how AβOs may activate neuronal PANoptosis by causing mitochondrial dysfunction during the development of AD, providing guidance for the development of targeted neuronal treatment strategies.

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“…Oxidative stress is considered a critical element of the pathogenic process in AD, 39,40 and several studies have identified direct physical connections between many proteins associated with AD pathogenesis and mitochondria or mitochondrial proteins (Figure 2). 34,41 Small molecules are substances that have the ability to interact with a wide range of biological targets, including proteins, enzymes, receptors, and genes. By modifying the activity or functionality of certain targets, they can have therapeutic effects.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Small-molecules against Oxidative stress mediated Neurodegenerative diseases

Pal

2023

CBL

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Neurodegenerative diseases, marked by the gradual deterioration of neuronal structure and function, impose a significant burden on global healthcare systems. Oxidative stress, resulting from an imbalance between reactive oxidant production and cellular antioxidant defense, is believed to play a significant role in the development of various neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Recently, there has been a growing interest in exploring small compounds as potential therapeutic agents to counteract oxidative stress. In addition to highlighting the potential of small molecules to prevent oxidative stress-mediated neuronal damage, this article provides an overview of the function of oxidative stress in neurodegenerative illnesses. Targeting numerous oxidative stressrelated pathways, a number of small molecules, including both natural and synthetic antioxidants, have shown promise for neuroprotective benefits. These substances neutralise reactive oxidants, boost endogenous antioxidant defences, reduce inflammation, alter mitochondrial function, and encourage neurotrophic growth.

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The contribution of mitochondria-associated endoplasmic reticulum membranes (MAMs) dysfunction in Alzheimer’s disease and the potential countermeasure

Cited by 9 publications

References 68 publications

Alzheimer’s-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets

Alzheimer’s-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets

Neurotoxic β-amyloid oligomers cause mitochondrial dysfunction—the trigger for PANoptosis in neurons

Small-molecules against Oxidative stress mediated Neurodegenerative diseases

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