Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India.
Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, 142001, India.
Neurosci Lett. 2021 May 14;753:135873. doi: 10.1016/j.neulet.2021.135873. Epub 2021 Apr 1.
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.
帕金森病（PD）是一种进行性神经退行性疾病，源于黑质致密部（SNpc）多巴胺能神经元的退化。多巴胺能神经的丧失和多巴胺的缺乏导致运动症状，表现为僵硬、震颤和运动迟缓。重金属和微量元素在神经系统中发挥着各种生理和病理作用。过量接触汞（Hg）、铅（Pb）、铜（Cu）、锌（Zn）、铁（Fe）、锰（Mn）、铝（Al）、砷（As）、镉（cd）和硒（Se）等有毒金属会穿过血脑屏障进入大脑，导致多巴胺能神经元变性。大脑中重金属的浓度过高会促进氧化应激、线粒体功能障碍和α-突触核蛋白的形成，导致多巴胺能神经元损伤。越来越多的证据表明，人体内正常存在的痕量重金属也会导致自由基的形成和积累，从而影响基底神经节信号。在这篇综述中，我们探讨了这些金属如何影响大脑生理学及其在有毒蛋白（α-突触核蛋白和路易小体）积累中的作用。我们还讨论了与神经毒性作用相关的金属及其作为 PD 管理的预防措施。我们的目标是提高人们对金属在 PD 发病和进展中的作用的认识。
