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Br J Pharmacol. 2019 Jan 24. doi: 10.1111/bph.14585
Abstract
Cell bioenergetic dysfunction is a common feature in neurodegenerative diseases, the most common of which is Alzheimer's disease (AD). Disrupted energy utilization implicates mitochondria at its nexus. This review summarizes some of the evidence that points to faulty mitochondrial function in AD and highlights past and current therapeutic development efforts.
Classical neuropathological hallmarks of disease (Aβ, tau) and sporadic AD risk genes (APOE) may trigger mitochondrial disturbance, yet mitochondrial dysfunction may incite pathology. Preclinical and clinical efforts have overwhelmingly centered on the amyloid pathway, but clinical trials have yet to reveal clear-cut benefits.
AD therapeutics aimed at mitochondrial dysfunction are few, and concentrate on reversing oxidative stress and cell death pathways. Novel research efforts aimed at boosting mitochondrial and bioenergetic function offer an alternative treatment strategy. Enhancing cell bioenergetics in preclinical models may yield widespread favorable effects that could benefit persons with AD.
Abstract
Cell bioenergetic dysfunction is a common feature in neurodegenerative diseases, the most common of which is Alzheimer's disease (AD). Disrupted energy utilization implicates mitochondria at its nexus. This review summarizes some of the evidence that points to faulty mitochondrial function in AD and highlights past and current therapeutic development efforts.
Classical neuropathological hallmarks of disease (Aβ, tau) and sporadic AD risk genes (APOE) may trigger mitochondrial disturbance, yet mitochondrial dysfunction may incite pathology. Preclinical and clinical efforts have overwhelmingly centered on the amyloid pathway, but clinical trials have yet to reveal clear-cut benefits.
AD therapeutics aimed at mitochondrial dysfunction are few, and concentrate on reversing oxidative stress and cell death pathways. Novel research efforts aimed at boosting mitochondrial and bioenergetic function offer an alternative treatment strategy. Enhancing cell bioenergetics in preclinical models may yield widespread favorable effects that could benefit persons with AD.