Beyond the brain: ?-Synuclein and its implications in bone and fat metabolism

Abstract

Introduction: Pathological form of α-synuclein is the major component of the Lewy body in the brain of Parkinson’s disease (PD) patients. Research efforts have been directed towards understanding the root and progression of the neurodegeneration and its association to symptoms. Physiological α-synuclein is ubiquitously present in the human body, however, its role outside the central nervous system has been poorly studied. PD seriously impairs life quality; symptoms comprehend from locomotor dysfunction including resting tremors, rigidity and bradykinesia to non-motor features such as autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep and sensory disorders. Additionally, PD patients often experiment weight loss, impaired bone mineral density and increased risk of fracture, which severity increases as the disease progresses. Recently, we have found that α-synuclein is a novel and key regulator of bone homeostasis. Moreover, we showed in mice that absence of α-synuclein partially protects against bone loss induced by estrogen-deficiency and weight gain. Our central hypothesis is that α-synuclein exerts these effects by acting cell autonomously in fat and bone cells, thus, our work aims to improve the understanding of α-synuclein regulating body fat mass and bone health to shed light of potential therapeutic targets