Metals associated neurodegeneration in Parkinson's disease: Insight to physiological, pathological mechanisms and management

Abstract

Parkinson's disease (PD) is a deliberately progressive neurological disorder, arises due to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of dopaminergic nerves and dopamine deficiency leads to motor symptoms characterized by rigidity, tremor, and bradykinesia. Heavy metals and trace elements play various physiological and pathological roles in the nervous system. Excessive exposure to toxic metals like mercury (Hg), lead (Pb), copper (Cu), zinc (Zn), iron (Fe), manganese (Mn), aluminium (Al), arsenic (As), cadmium(cd), and selenium (Se) cross the blood-brain barrier to enter into the brain and leads to dopaminergic neuronal degeneration. Excessive concentrations of heavy metals in the brain promote oxidative stress, mitochondrial dysfunction, and the formation of α-synuclein leads to dopaminergic neuronal damage. There is increasing evidence that heavy metals normally present in the human body in minute concentration also cause accumulation to initiate the free radical formation and affecting the basal ganglia signaling. In this review, we explored how these metals affect brain physiology and their roles in the accumulation of toxic proteins (α-synuclein and Lewy bodies). We have also discussed the metals associated with neurotoxic effects and their prevention as management of PD. Our goal is to increase the awareness of metals as players in the onset and progression of PD.

Keywords: Alpha-synuclein; Chelating agents; Heavy metals; Parkinson’s disease; Substantia nigra.