Formation of Lewy body inclusions (LBs) in the substantia nigra (SN) is a very well-characterized pathol. hallmark of Parkinson′s disease (PD).LBs are aggregates of many biol. inactive proteins including structural elements, alpha-synuclein (asyn)-binding proteins, synphilin-1-binding proteins, and components of the ubiquitin-proteasome system, proteins implicated in cellular responses, proteins associated with phosphorylation and signal transduction, cytoskeletal proteins, cell cycle proteins, cytosolic proteins and many more.So far almost 76 proteins have been found to be associated with the formation of LBs.Deposition of LBs in the cell bodies and neurites often leads to the metabolic impairment and eventually the death of dopaminergic (DA) neurons.Therefore, lowering the burden of LBs is a potential challenge to restore the health and function of DA neurons.The most important strategy for minimizing the accumulation of LBs is preserving mitochondrial homeostasis.In a healthy neuron, mitochondrial biogenesis (mitogenesis) is required for the production of ATP, neurotransmitter release, calcium buffering, and augmentation of synaptic strength.However, during neurodegenerative condition, increased mitogenic response might bring opposite effect as it leads to the production of more depolarized mitochondria, reactive oxygen species (ROS), different inflammatory mediators including p38MAPK, Ras, Raf; and eventually the development of LB pathol.Therefore, tight regulation between mitochondrial biosynthesis and its breakdown is critical for the maintenance of neuronal health and function.Recently, our lab has delineated the role of a novel ankyrin-rich, BTB domain containing protein BPOZ-2 or ABTB2 in LB disease, which can also be a crucial regulator of mitochondrial quality control process.Our current perspective highlights the importance of BPOZ-2 inregulating mitochondrial damage control process and its therapeutic prospect in the treatment of LB disease.
