Neuroprotective Epigenetic and DNA Damage Repairing Molecular Mechanisms of L-Carnitine and its Congeners against Aging and Age-Related Neurodegenerative Diseases

Abstract

Aging is an ubiquitous biological phenomena characterized by ever-increasing susceptibility to diseases due to increased oxidative stress (OS) and an ultimate severe non-repairable membrane molecular and mitochondrial damages coupled with energy (ATP) depletion. L-Carnitine (β-hydroxy-γ-trimethyl amino butyrate) and its congeners plays an essential role in mitochondrial ATP synthesis while being a powerful anti-inflammatory antioxidant and an organic, non-ionic bi-phasic osmolytes. L-carnitine exerts antimutagenic and genome stabilizing effects by increasing mitochondrial metabolism, anneals DNAstrand breaks and enhances genome stability by modulating histones and DNA-repairing enzymes. Poly (ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme and normally functions in DNA damage repair mechanism acts as a double-edged sword, which anneals mild repairable DNA damages, but extensive PARP-1 activation can promote cell death through processes involving energy depletion in severe OS. It has been reported that, severe oxidative stress-mediated extensive non-repairable DNA damage can over-activate PARP-1 and consumes enormous NAD + and consequently ATP, culminating in cell dysfunction or necrosis by autocatalysis of PARP-1 and caspases. The DNA damage associated with OS known to activate DNA repair proteins, including PARP-1, an important biomarker of brain aging and age-related neurodegenerative diseases. This study delineates the neuroprotective epigenetic and DNArepairing molecular mechanisms of the iron-chelating anti-inflammatory genome stabilizing antioxidant ergogenic aid L-Carnitine and its congeners against selected degenerative diseases such as Parkinson's disease (PD), Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS) and Multiple sclerosis (MS).

L-Carnitine Prevents Behavioural Alterations in Ketamine-Induced Schizophrenia in Mice: Possible Involvement of Oxidative Stress and Inflammation Pathways

“…L-Carnitine (l-car) is required for β-oxidation of longchain fatty acids in mitochondria [19]. It also showed antioxidant properties, such as boosting the antioxidant system [20], preventing lipid peroxidation [21], protecting DNA and cell membranes from damage caused by ROS [22,23], helping to normalize age-related changes [24,25], and also increasing the immune system's ability [26]. Furthermore, some recent studies have reported the anti-infammatory [27] and neuroprotective [28,29] efects of l-car and its positive efects on some diseases [30,31].…”

Sense an Elusive Threat-(Now Old Age Has Nowhere To Hide)

“…Aging is a ubiquitous biological phenomena, characterized by ever-increasing susceptibility to diseasesmitochondrial damages, and ultimately death. (8) Aging is an ubiquitous biological phenomena characterized by ever-increasing susceptibility to diseases due to increased oxidative stress (OS). (9) Current evidence suggests both resveratrol and pterostilbene may be modulators for agedrelated neurodegeneration, obese, diabetes, and cardiovascular diseases.…”