TITLE:
Mitochondrial Dysfunction and Alzheimer’s Disease
AUTHORS:
Fatimah M. Albrekkan, Marie Kelly-Worden
KEYWORDS:
Alzheimer’s; Mitochondria; Cybrid; Oxidative Stress
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.3 No.2A,
May
20,
2013
ABSTRACT: Alzheimer’s disease (AD) is a
neurodegenerative disorder that is characterized by progressive loss of basal
forebrain cholinergic neurons, leading to reduction in transmission through
cholinergic fibers involved in processes of attention, learning, and memory.
Mitochondria provide and regulate cellular energy and are crucial for proper
neuronal activity and survival. Mitochondrial dysfunction is evident in early
stages of AD and is involved in AD pathogenesis. This review focuses on the
evidence supporting a clear association between amyloid-β toxicity,
mitochondrial dysfunction, oxidative stress and neuronal damage/death in
Alzheimer’s disease. To date, the beta amyloid (Aβ) cascade hypothesis
still remains the main pathogenetic model of Alzheimer’s disease (AD), but its
role in the majority of sporadic AD cases is uncertain. Furthermore, the
“mitochondrial cascade hypothesis” could explain many of the biochemical, genetic, and pathological features of
sporadic AD. This hypothesis promotes mutations in mitochondrial DNA (mtDNA) as
the basis for Alzheimer’s disease. The mutations could lead to energy failure,
increased oxidative stress, and accumulation of Aβ, which in a vicious
cycle reinforces the mtDNA damage and oxidative stress.