Palash Mandal

By Farhin Patel and Palash Mandal

In the world, 3.3 million deaths occur every year due to harmful use of alcohol; this represents 5.9% of all deaths. Ethanol metabolites’ production and their post-translation modification are one of the proposed mechanisms that lead to neuronal toxicity. The projected neurochemical changes in chronic alcohol drinkers may be due to an imbalance between excitatory and inhibitory neurotransmitters. Interaction of alcohol with GABA and glutamate receptors (NMDA and AMPA) resulted in diverse adaptive changes in gene expression through neuronal pathways leading to alcohol toxicity. Alcohol consumption in an individual leads to biochemical changes that are correlated with complex inflammatory signaling pathways such as phosphorylation of proteins, synthesis of nitric oxide (NO), NF-kappaB and MAP kinase pathways in certain regions of the brain. Ethanol exposure activates neurons and microglial cells that lead to release of neuroimmune factors like high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4) and certain cytokines involved in immune responses leading to neuroimmune signaling in the brain. Epigenetic modification of DNA and histones may lead to neuronal gene expression, thus regulating ethanol toxicity. Researchers attempt to modulate therapies that can help to foil alcohol toxicity and support the development of original neuronal cells that have been injured or degenerated by alcohol exposure.

Part of the book: Drug Addiction

By Farhin Patel and Palash Mandal

Alzheimer’s disease and Parkinson’s disease are characterized as a chronic and progressive neurodegenerative disorder and are manifested by the loss of neurons within the brain and/or spinal cord. In the present chapter, we would like to summarize the molecular mechanism focusing on metabolic modification associated with neurodegenerative diseases or heritable genetic disorders. The identification of the exact molecular mechanisms involved in these diseases would facilitate the discovery of earlier pathophysiological markers along with substantial therapies, which may consist (of) mitochondria-targeted antioxidant therapy, mitochondrial dynamics modulators, epigenetic modulators, and neural stem cell therapy. Therefore, all these therapies may hold particular assurance as influential neuroprotective therapies in the treatment of neurodegenerative diseases.

Part of the book: Neurons

By Dhara Patel and Palash Mandal

Adipose tissue comprises of large volumes of biologically functioning fat globule, which employs substantial systemic effect. Adipocytes and adipokines play an active role in autocrine, paracrine, or endocrine metabolic functions. Recent studies demonstrated that the hormonal role of adipocyte and adipose tissue dysfunction contributes to the pathogenesis of alcoholic liver disease (ALD) by the activation of CYP2E1. The gut microbiome and adipose tissue response play a pivotal role in the pathogenesis of ALD. Enteric dysbiosis increases plasma levels of metabolites that activate Kupffer cells. Recent literature suggested that chronic alcohol consumption is also correlated with oxidative stress in adipose tissue, inflammation, and adipocyte cell death, decrease in adiponectin, increase level of leptin and resistin, adipose tissue mass, and insulin resistance that acts on the muscle and liver. Dysbiosis combined with non-nutritional diet has an effect on the luminal metabolism causing immunological changes in the gut that might also contribute to pathogenesis of nonalcoholic fatty liver disease (NAFLD). Understanding the interaction between the altered gut microbiota, diet, environmental factors, and their effects on the gut-liver axis can provide an insight toward the pathogenesis of liver-associated disease.

Part of the book: Adipose Tissue