Mitochondrial dysfunction and axon degeneration in progressive multiple sclerosis

Abstract

The neuron is the target of inflammatory demyelinating processes in multiple sclerosis (MS). In progressive MS, however, there is a gathering body of evidence indicating that molecular changes converge on mitochondria within neuronal cell bodies. The most reproducible change relates to mitochondrial respiratory chain complex deficiency, which compromises the capacity of neurons to generate ATP. The resulting energy failure state is coupled with an increase in demand for energy by the demyelinated axon, being particularly relevant to the long tracts such as corticospinal tracts with long projection axons. Recent work in our laboratory and that of our collaborators indicates the limited reflection of the mitochondria changes within neurons in experimental disease models. The mitochondrial changes within neuronal compartments are likely to offer novel targets for the improvement in neuronal function in patients with progressive MS.

Melatonin multiple effects on brown adipose tissue molecular machinery

“…It is also important to notice the impact of melatonin absence in the pathophysiologic level, as mitochondrial deficiencies or activity reduction of its complexes is constantly attached to the emergence of several diseases . With a well‐defined role in damage prevention, apoptosis, and oxidative stress in these organelles, melatonin has an important role in disease prevention …”

“…It is also important to notice the impact of melatonin absence in the pathophysiologic level, as mitochondrial deficiencies or activity reduction of its complexes is constantly attached to the emergence of several diseases. [83][84][85] With a well-defined role in damage prevention, apoptosis, and oxidative stress in these organelles, melatonin has an important role in disease prevention. [86][87][88] The results seen in Ucp1 gene and protein expressions in PINX animals are possibly due to time disorganization of the transcription factors Pgc1α and Cidea expression, which presented rhythmicity in this group, differently from the observed in the other groups.…”

The Axon-Myelin Unit in Development and Degenerative Disease

“…Mechanistically, this is likely related to axonal energy deficits, as nitric oxide and reactive oxygen species can damage mitochondrial respiratory chain complexes (reviewed in Smith and Lassmann, 2002 ). Indeed, a deficiency in complex IV function in axons (Mahad et al, 2009 ) and neuronal cell bodies (reviewed in Campbell and Mahad, 2018 ) in MS has been reported, although the causes and consequences in the disease context are as yet unproven.…”

On the Neuroprotective Role of Astaxanthin: New Perspectives?

“…The release of pro-inflammatory mediators, together with pro-oxidant agents, results in morphological and functional changes of intracellular organelles and contributes to the insurgence and progression of neurodegenerative pathologies. An example are mitochondria, intracellular targets of oxidative injuries, where chronic inflammation could produce mitochondrial dysfunction [38,39,40]. …”