Potential Therapeutic Benefits of Maintaining Mitochondrial Health in Peripheral Neuropathies

Abstract

Background: Peripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy. Method: The current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of maintaining a healthy mitochondrial environment in neuronal cells via pharmacological management in context of peripheral neuropathies. Results: Aberrant cellular signaling coupled with changes in neurotransmission, peripheral and central sensitization are found to be responsible for the pathogenesis of variant toxic neuropathies. Current research reports have indicated the possible involvement of mitochondria mediated redox imbalance as one of the principal causes of neuropathy aetiologies. In addition to imbalance in redox homeostasis, mitochondrial dysfunction is also responsible for alterations in physiological bioenergetic metabolism, apoptosis and autophagy pathways. Conclusions: In spite of various etiological factors, mitochondrial dysfunction has been found to be a major pathomechanism underlying the neuronal dysfunction associated with peripheral neuropathies. Pharmacological modulation of mitochondria either directly or indirectly is expected to yield therapeutic relief from various primary and secondary mitochondrial diseases.

Melatonin prevents mitochondrial dysfunction and promotes neuroprotection by inducing autophagy during oxaliplatin‐evoked peripheral neuropathy

“…Given the pathological role of oxidative/nitrosative stressmediated mitochondrial dysfunction and perturbations in autophagy in peripheral neuropathy, studies that explore pharmacological agents that may promote autophagy and maintain mitochondrial homeostasis have garnered much interest. 9,10,22 Herein, our study reveals in vitro and in vivo neuroprotective mechanisms of melatonin against oxaliplatin-induced neurotoxicity. The results suggest that melatonin efficiently prevents mitochondrial dysfunction and neuronal apoptosis by virtue of its antioxidant effects and has the ability to improve autophagy in oxaliplatin-induced neurotoxicity.…”

“…Given the pathological role of oxidative/nitrosative stress‐mediated mitochondrial dysfunction and perturbations in autophagy in peripheral neuropathy, studies that explore pharmacological agents that may promote autophagy and maintain mitochondrial homeostasis have garnered much interest . Herein, our study reveals in vitro and in vivo neuroprotective mechanisms of melatonin against oxaliplatin‐induced neurotoxicity.…”

“…Oxidative/nitrosative stress in peripheral nerves and DRG may be an important underlying and interconnected pathomechanism with mitochondrial dysfunction, inflammation, and apoptosis leading to neurodegeneration. The mitotoxicity hypothesis posits that oxaliplatin causes mitochondrial injury with swelling and vacuolation leading to abnormal spontaneous discharges and compartment degeneration in somatosensory primary afferent neurons . Whilst several antioxidant treatments for chemotherapy‐induced neuropathy have been tested and include n‐acetylcysteine, n‐acetyl carnitine, glutathione, alpha‐lipoic acid, and vitamin E, but have been shown to have limited efficacy, due to their inability to modify redox signaling pathways .…”

“…The mitotoxicity hypothesis posits that oxaliplatin causes mitochondrial injury with swelling and vacuolation leading to abnormal spontaneous discharges and compartment degeneration in somatosensory primary afferent neurons. 10,11 Whilst several antioxidant treatments for chemotherapy-induced neuropathy have been tested and include n-acetylcysteine, n-acetyl carnitine, glutathione, alpha-lipoic acid, and vitamin E, 8,12 but have been shown to have limited efficacy, 13 due to their inability to modify redox signaling pathways. 14 Hence, therapeutic interventions that simultaneously prevent oxidative/ nitrosative stress associated with mitochondrial dysfunction and maintain the bioenergetic status of the neuron may have therapeutic potential in the treatment of oxaliplatin-induced neuropathy.…”

A Network Pharmacology Approach for the Identification of Common Mechanisms of Drug‐Induced Peripheral Neuropathy

“…31,32 Some mechanisms involving changes in mitochondrial movement, abnormal distribution, 33 and perturbations in mitochondrial fission 34 in CMT have been associated with mutations of GDAP1. Our results may provide a starting point for further exploration of therapies targeting mitochondrial processes, 35 which might have beneficial effects in the treatment of DIPN.…”