Title:Mitochondrially-Targeted Therapeutic Strategies for Alzheimer’s Disease
Volume: 18
Issue: 10
Author(s): Isaac G. Onyango*, James P. Bennett and Gorazd B. Stokin
Affiliation:
- Centre for Translational Medicine International Clinical Research Centre, St. Anne’s University Hospital CZ-65691, Brno,Czech Republic
Keywords:
Alzheimer's disease, mitochondria, mtDNA, bioenergetics, β-amyloid, epigenetic modifiers, lifestyle changes,
repurposed drugs.
Abstract: Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative disease and
the most common cause of dementia among older adults. There are no effective treatments available
for the disease, and it is associated with great societal concern because of the substantial costs
of providing care to its sufferers, whose numbers will increase as populations age. While multiple
causes have been proposed to be significant contributors to the onset of sporadic AD, increased age
is a unifying risk factor. In addition to amyloid-β (Aβ) and tau protein playing a key role in the initiation
and progression of AD, impaired mitochondrial bioenergetics and dynamics are likely major
etiological factors in AD pathogenesis and have many potential origins, including Aβ and tau. Mitochondrial
dysfunction is evident in the central nervous system (CNS) and systemically early in the
disease process. Addressing these multiple mitochondrial deficiencies is a major challenge of mitochondrial
systems biology. We review evidence for mitochondrial impairments ranging from mitochondrial
DNA (mtDNA) mutations to epigenetic modification of mtDNA, altered gene expression,
impaired mitobiogenesis, oxidative stress, altered protein turnover and changed organelle dynamics
(fission and fusion). We also discuss therapeutic approaches, including repurposed drugs,
epigenetic modifiers, and lifestyle changes that target each level of deficiency which could potentially
alter the course of this progressive, heterogeneous Disease while being cognizant that successful
future therapeutics may require a combinatorial approach.
