Mitochondrial dysfunction in psychiatric and neurological diseases: Cause(s), consequence(s), and implications of antioxidant therapy

Abstract

Mitochondrial dysfunction is at the base of development and progression of several psychiatric and neurologic diseases with different etiologies. MtDNA/nDNA mutational damage, failure of endogenous antioxidant defenses, hormonal malfunction, altered membrane permeability, metabolic dysregulation, disruption of calcium buffering capacity and ageing have been found to be the root causes of mitochondrial dysfunction in psychatric and neurodegenerative diseases. However, the overall consequences of mitochondrial dysfunction are only limited to increase in oxidative/nitrosative stress and cellular energy crises. Thus far, extensive efforts have been made to improve mitochondrial function through specific cause-dependent antioxidant therapy. However, owing to complex genetic and interlinked causes of mitochondrial dysfunction, it has not been possible to achieve any common, unique supportive antioxidant therapeutic strategy for the treatment of psychiatric and neurologic diseases. Hence, we propose an antioxidant therapeutic strategy for management of consequences of mitochondrial dysfunction in psychiatric and neurologic diseases. It is expected that this will not only reduces oxidative stress, but also promote anaerobic energy production.

Epigenetic Treatment of Neuropsychiatric Disorders: Autism and Schizophrenia

“…SCZ, like ASD, is also associated with mitochondrial dysfunction [Bubber et al, ; Clay et al, ; Kasote et al, ; Rajasekaran et al, ]. SCZ is characterized by cognitive impairment, dulling of affect, and disturbance in reality testing (psychosis) as evidenced by symptoms such as hallucinations and delusions [van Os and Kapur, ; McClellan et al, ; Howes and Murray, ].…”

“…PMX‐500FI, an α‐lipoic acid (ALA) carnitine‐conjugated ester (Fig. ) [Steliou et al, ; Gorąca et al, ; Keith et al, ; Zaitone et al, ; Kasote et al, ; Fernández‐Galilea et al, ], was more effective at protecting neurons from apoptotic and necroptotic cell death in the substantia nigra pars compacta [Foradori, Hoffman and Irwin, unpublished data], likely due to active mitochondria‐delivery (and thus, enhanced bioavailability [Steliou et al, ]), than an equimolar amount of ALA and l ‐carnitine mixed together. PMX‐550B, a butyrate carnitinoid (Fig.…”

“…ALA and MitoQ (a mitochondria‐targeting lipoic acid derivative) are powerful antioxidants that attenuate neurotoxicity by modulating the proapoptotic effector BAX (a protein that translocates from the cytosol to the mitochondria [Thornton and Hagberg, ]) [Kasote et al, ; Dixit et al, ; Fernández‐Moriano et al, ; Najafi et al, ]. Lipoic acid is necessary for the recycling of vitamins C and E and glutathione [Liu, ].…”

Evaluation of Antioxidant potential of the Siddha Formulation Sambirani Poo Kuligai by in-vitro DPPH radical scavenging assay

“…Since then, the antioxidant potential of plants has received a great deal of attention because increased oxidative stress has been identified as a major causative factor in the development and progression of several life threatening diseases, including neurodegenerative and cardiovascular disease. In addition, supplementation with exogenous antioxidants or boosting of endogenous antioxidant defenses of the body has been found to be a promising method of countering the undesirable effects of oxidative stress [5]. Siddha system of medicine pioneering in emphasize the biological activity of the various phytocomponents with respect to the etiology and pathophysiology of various dread full disease emerging in humans and animals.…”

Improvement of Oxidative and Metabolic Parameters by Cellfood Administration in Patients Affected by Neurodegenerative Diseases on Chelation Treatment

“…Mitochondrial dysfunction is considered to be the basis of the development and progression of several neurologic diseases with different aetiologies, including ND [8]. Therefore, mitochondria have become an interesting target of drug therapy [9].…”