Design, synthesis and study of molecular probes for diagnostic and therapeutic applications in Alzheimer's disease

Abstract

"The process of protein misfolding and aggregation has been a prime subject of research. This process is identified in the main pathological event involved in several diseases like Alzheimer’s disease (AD), Parkinson disease (PD), Huntington disease (HD), Type II diabetes (T2D) and prion-related disorders among others.1-3 AD is the most prevalent form of neurodegenerative diseases causing progressive attrition of cognition, task performance ability, mood, speech, behaviour and memory.4,5,6 A recent report from the National Center for Health Statistics (NCHS), USA suggests that deaths caused by diseases like ischemic heart disease, brain stroke, AIDS (acquired immune deficiency syndrome) and cancer have decreased significantly, while deaths caused by AD is on a constant rise.7 Alarmingly, in the next decade AD is likely to become particularly devastating for the poor and developing countries, severely affecting their public health and economy.8 For this reason, both scientific and clinical research community is putting tremendous efforts into understanding the disease to develop molecular tools for early diagnosis and cure. AD involves two major types of misfolded protein aggregates: intracellular aggregates of the microtubule-associated tau protein (called neurofibrillary tangles - NFT) and extracellular peptide aggregates known as senile plaques, mainly composed of amyloid  (Aβ) peptides.9 Aβ peptides are transmembrane peptides produced by incorrect processing of the integral membrane protein called amyloid precursor protein (APP).10 The physiological function of Aβ peptide in normal brain is not completely understood, although it is said to be playing a vital role in neurogenesis and modulation of synaptic plasticity.11"