The role of mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease and future strategies for targeted therapy DOI Creative Commons
Xin Li,

Ziyang Wu,

X.C. Si

и другие.

European journal of medical research, Год журнала: 2025, Номер 30(1)

Опубликована: Май 31, 2025

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, behavioral impairments, and psychiatric comorbidities. The pathogenesis of AD remains incompletely elucidated, despite advances in dominant hypotheses such as the β-amyloid (Aβ) cascade, tauopathy, cholinergic deficiency, neuroinflammation mechanisms. However, these inadequately explain multifactorial nature AD, which exposes limitations our understanding its Mitochondrial dysfunction known to play pivotal role since patients exhibit intracellular mitochondrial structural changes brain at an early stage, correcting imbalance homeostasis cytopathological caused it may be potential target for treatment AD. abnormalities accelerate pathogenesis. For instance, functional alterations mitochondria-associated endoplasmic reticulum membrane (MAM) can disrupt Ca2⁺ cholesterol metabolism, consequently promoting Aβ accumulation. In addition, overaccumulation hyperphosphorylated tau proteins further damage neurons disrupting integrity mitophagy, thereby amplifying pathological aggregation exacerbating neurodegeneration Furthermore, deposition abnormal dynamics through dysregulation fission/fusion proteins, leading excessive fragmentation subsequent dysfunction. Additionally, impair transport, resulting axonal This article reviews biological significance morphology, dynamics, DNA (mtDNA) instability pathology, emphasizing mitophagy critical contributor progression. biogenesis proteostasis are maintaining function integrity. Impairments processes have been implicated progression highlighting multifaceted neurodegeneration. It discusses therapeutic mitochondria-targeted strategies drug development.

Язык: Английский

The role of mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease and future strategies for targeted therapy DOI Creative Commons
Xin Li,

Ziyang Wu,

X.C. Si

и другие.

European journal of medical research, Год журнала: 2025, Номер 30(1)

Опубликована: Май 31, 2025

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, behavioral impairments, and psychiatric comorbidities. The pathogenesis of AD remains incompletely elucidated, despite advances in dominant hypotheses such as the β-amyloid (Aβ) cascade, tauopathy, cholinergic deficiency, neuroinflammation mechanisms. However, these inadequately explain multifactorial nature AD, which exposes limitations our understanding its Mitochondrial dysfunction known to play pivotal role since patients exhibit intracellular mitochondrial structural changes brain at an early stage, correcting imbalance homeostasis cytopathological caused it may be potential target for treatment AD. abnormalities accelerate pathogenesis. For instance, functional alterations mitochondria-associated endoplasmic reticulum membrane (MAM) can disrupt Ca2⁺ cholesterol metabolism, consequently promoting Aβ accumulation. In addition, overaccumulation hyperphosphorylated tau proteins further damage neurons disrupting integrity mitophagy, thereby amplifying pathological aggregation exacerbating neurodegeneration Furthermore, deposition abnormal dynamics through dysregulation fission/fusion proteins, leading excessive fragmentation subsequent dysfunction. Additionally, impair transport, resulting axonal This article reviews biological significance morphology, dynamics, DNA (mtDNA) instability pathology, emphasizing mitophagy critical contributor progression. biogenesis proteostasis are maintaining function integrity. Impairments processes have been implicated progression highlighting multifaceted neurodegeneration. It discusses therapeutic mitochondria-targeted strategies drug development.

Язык: Английский

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