Title:Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders
Volume: 18
Issue: 1
Author(s): Kenneth Maiese*
Affiliation:
- Cellular and Molecular Signaling, New York, NY 10022,United Arab Emirates
Keywords:
Alzheimer's disease, AMP activated protein kinase (AMPK), autophagy, apoptosis, dementia, diabetes mellitus,
forkhead transcription factors, FoxO, mechanistic target of rapamycin (mTOR), oxidative stress, silent mating type information
regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), sirtuin, stem cells.
Abstract: Neurodegenerative disorders impact more than one billion individuals worldwide and
are intimately tied to metabolic disease that can affect another nine hundred individuals throughout
the globe. Nicotinamide is a critical agent that may offer fruitful prospects for neurodegenerative
diseases and metabolic disorders, such as diabetes mellitus. Nicotinamide protects against multiple
toxic environments that include reactive oxygen species exposure, anoxia, excitotoxicity, ethanolinduced
neuronal injury, amyloid (Aß) toxicity, age-related vascular disease, mitochondrial dysfunction,
insulin resistance, excess lactate production, and loss of glucose homeostasis with pancreatic
β-cell dysfunction. However, nicotinamide offers cellular protection in a specific concentration
range, with dosing outside of this range leading to detrimental effects. The underlying biological
pathways of nicotinamide that involve the silent mating type information regulation 2 homolog 1
(Saccharomyces cerevisiae) (SIRT1), the mechanistic target of rapamycin (mTOR), AMP activated
protein kinase (AMPK), and mammalian forkhead transcription factors (FoxOs) may offer insight
for the clinical translation of nicotinamide into a safe and efficacious therapy through the modulation
of oxidative stress, apoptosis, and autophagy. Nicotinamide is a highly promising target for the
development of innovative strategies for neurodegenerative disorders and metabolic disease, but
the benefits of this foundation depend greatly on gaining a further understanding of nicotinamide’s
complex biology.
