Chapter 9 - Disarrayed mitochondrial function on pathobiology in Down syndrome and targeted therapeutics

Abstract

Indeed, trisomic HSA21 underlies the genome-wide gene deregulation contributing to variability of Down syndrome (DS) phenotypes. In fact, the pathomechanism at cellular and systemic levels is directly set off by the interplay between specific changes in HSA21-gene expression operating on a background of generalized metabolic perturbations. Albeit conceptions with DS have a high rate of pregnancy loss or die early in postnatal life, still this aneuploidy has exhibited extended life span beyond 60 years. However, myriads of DS clinical phenotypes, including intellectual disability, early aging and neurodegeneration, and Alzheimer disease (AD)-related dementia, are inevitable where mitochondrial dysfunctions play the central role. Collectively, the mitochondrial abnormalities and altered energy metabolism are responsible for neuronal defects, learning disability, heart defects, hypotonia, AD, type 2 diabetes, obesity, immune disorders, and so on. Mitochondrial stress can also confer adaptive response at a low level; however, impaired scavenging of free radicals may disturb mitophagy. Therefore, therapeutic amelioration of the mitochondrial defects was targeted to improve the quality of life of DS individuals and their families. A number of pharmacologically active compounds, including natural bio-elements, have shown a convincing outcome for correction of mitochondrial dysfunctions and dysfunctional oxidative metabolism.