Brain insulin resistance and Parkinson’s disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Its most prominent pathological features are the loss of dopaminergic neurons in the substantia nigra pars compacta and the deposition of intraneuronal inclusions named Lewy bodies. Currently, the pathophysiological mechanisms of PD are not fully understood. Growing evidence suggests that insulin resistance, diabetes and PD share similar pathological processes. This raises the possibility that defective insulin signaling pathways contribute to the occurrence and development of PD. In this article, we firstly reviewed the evidence of insulin resistance from epidemiology, PD patients and animal models. We also explained the insulin signal pathways in central nervous system. We then showed the evidence that insulin resistance participates in the pathogenesis of PD via protein aggregation, mitochondrial dysfunction, neural inflammation and cognitive impairment. Finally, we introduced four categories of drugs that facilitate insulin signaling and their effects on neurodegeneration in PD.

Keywords

Parkinson’s disease (PD) / diabetes / insulin resistance / α-synuclein (α-syn) / mitochondrial dysfunction / neural inflammation