Mitochondrion-Specific Antioxidants as Drug Treatments for Alzheimer Disease

Abstract

Age-related dementias such as Alzheimer disease (AD) have been linked to vascular disorders like hypertension, diabetes and atherosclerosis. These risk factors cause ischemia, inflammation, oxidative damage and consequently reperfusion, which is largely due to reactive oxygen species (ROS) that are believed to induce mitochondrial damage. At higher concentrations, ROS can cause cell injury and death which occurs during the aging process, where oxidative stress is incremented due to an accelerated generation of ROS and a gradual decline in cellular antioxidant defense mechanisms. Neuronal mitochondria are especially vulnerable to oxidative stress due to their role in energy supply and use, causing a cascade of debilitating factors such as the production of giant and/or vulnerable young mitochondrion who's DNA has been compromised. Therefore, mitochondria specific antioxidants such as acetyl-L-carnitine and R-alphalipoic acid seem to be potential treatments for AD. They target the factors that damage mitochondria and reverse its effect, thus eliminating the imbalance seen in energy production and amyloid beta oxidation and making these antioxidants very powerful alternate strategies for the treatment of AD.

Mechanistic studies on ketamine-induced mitochondrial toxicity in zebrafish embryos

“…It plays a major role in the transport of long chain fatty acids into mitochondria that enter the β-oxidation cycle (Bohles et al, 1994). ALCAR effectively prevents mitochondrial injury resulting from oxidative damage (Palacios et al, 2011). Carnitines have neuroprotective effects on conditions associated with mitochondrial dysfunction, oxidative stress and possibly in neurodegenerative disorders (Beals et al, 2003).…”

L-Carnitine Protects Renal Tubular Cells Against Calcium Oxalate Monohydrate Crystals Adhesion Through Preventing Cells From Dedifferentiation

“…L-carnitine is a naturally occurring amino acid derivative synthesized in the liver and kidney, it acts as a carrier for fatty acids acrossing the inner mitochondrial membrane, which is necessary for subsequent β-oxidation and ATP production [9]. The compound has been considered as a specific inhibitor of mitochondrial reactive oxygen species (ROS) [10], and the beneficial effects of which to protect kidney cells against oxidative stress, lipid peroxidation, proinflammatory cytokines, and apoptosis during acute and chronic kidney injury have been documented [11][12][13]. These pathogenetic factors have also been reported to play pivotal part in renal stone formation [14].…”

Mitochondrial Permeability Transition Pore-as a Promising Target for Novel Neuroprotective Agents

“…Mitoprotective strategy for prevention of a series of neurodegenerative diseases, in particular, AD, being now one of the most promising approach in the development of neuroprotective drugs [2,3]. Aside from being an important source of cellular energy (ATP), mitochondria maintain the intracellular Ca 2+ levels within closely defined ranges for the mediation of signaling, control of neuronal excitability, and the synaptic function.…”