Abstract:

Aging is n 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-triethyl 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 DNA-strand 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 DNA-repairing 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).

Keywords: Aging, Neurodegenerative diseases, Oxidative stress, DNA damage, Poly (ADP-Ribose) polymerse-1, Caspase, ATP, L-Carnitine, Iron-Chelating Anti-inflammatory Antioxidants.

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