THE IMPORTANCE OF MOLECULAR CHAPERONES IN NEURODEGENERATIVE DISEASES

Abstract

Molecular chaperones are important in the maintenance of protein homeostasis and the elucidation of their functioning is necessary to verify their viability as a therapeutic target for neurodegenerative diseases. There is experimental evidence that these proteins, when induced, decrease the formation of protein aggregates that are formed by misfolded proteins that are characteristic of neurodegenerative diseases, such as amyloid β in Alzheimer's disease, α-synuclein in Parkinson's disease, and copper-zinc superoxide dismutase in amyotrophic lateral sclerosis. They are also known as heat shock proteins, because they are stress-induced proteins, but they are also constitutively expressed in smaller amounts, and often function as complexes exerting distinct functions. The context is complicated because in the formation of aggregates, the most toxic are not the largest and most compact, but the intermediates. So, when there is an error in the quality control of the proteins, the chaperone may not be able to finish the process of refolding or forwarding for degradation, and in fact, generate aggregates that are more toxic than the compacts that it has begun to break down. Thus, the inhibition of molecular chaperones may be therapeutic targets for the development of new drug therapies. Despite this, most scientific evidence shows improvement in the neurodegeneration through induction of these molecules.