Neurodegenerative diseases (NDDs) are heterogeneous group of disorders that lately become among the most life-threatening disorders affecting the elderly people. The neurodegenerative disorders that are collectively grouped under the term of tauopathies are featured by the presence of abundant neurofibrillary lesions made by accumulation of abnormal hyperphosphorylated microtubule associated protein tau inside the neurons and/or glial cells. Undoubtedly, tau protein plays a fundamental role in axonal microtubule network stabilization however, the flexible unfolded structure of tau enables modification of tau by several intracellular enzymes which in turn extends tau function and interaction spectrum. The distinctive characteristics of tau protein alongside the essential role of tau interaction partners in the development and progression of neuronal neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. This chapter aims to discuss interaction between mitochondria and tau, and the key molecular players that interfere with tau proteins in physiological and pathological conditions. We outline the putative molecular targets and address the mitochondrial critical role based on research efforts that previously identify their influence on diseases models. Taken together, no solitary player would trigger the whole pathogenic pathway, we attempted to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.
Keywords: Mitochondrial Complexes, Molecules, mTOR, PERK, Tauopathy, Targets.