Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India.
Pharmacy Practice Research Unit, Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.
Int J Mol Sci. 2022 Apr 20;23(9):4565. doi: 10.3390/ijms23094565.
Parkinson's disease (PD) refers to one of the eminently grievous, preponderant, tortuous nerve-cell-devastating ailments that markedly impacts the dopaminergic (DArgic) nerve cells of the midbrain region, namely the substantia nigra pars compacta (SN-PC). Even though the exact etiopathology of the ailment is yet indefinite, the existing corroborations have suggested that aging, genetic predisposition, and environmental toxins tremendously influence the PD advancement. Additionally, pathophysiological mechanisms entailed in PD advancement encompass the clumping of α-synuclein inside the lewy bodies (LBs) and lewy neurites, oxidative stress, apoptosis, neuronal-inflammation, and abnormalities in the operation of mitochondria, autophagy lysosomal pathway (ALP), and ubiquitin-proteasome system (UPS). The ongoing therapeutic approaches can merely mitigate the PD-associated manifestations, but until now, no therapeutic candidate has been depicted to fully arrest the disease advancement. Neuropeptides (NPs) are little, protein-comprehending additional messenger substances that are typically produced and liberated by nerve cells within the entire nervous system. Numerous NPs, for instance, substance P (SP), ghrelin, neuropeptide Y (NPY), neurotensin, pituitary adenylate cyclase-activating polypeptide (PACAP), nesfatin-1, and somatostatin, have been displayed to exhibit consequential neuroprotection in both in vivo and in vitro PD models via suppressing apoptosis, cytotoxicity, oxidative stress, inflammation, autophagy, neuronal toxicity, microglia stimulation, attenuating disease-associated manifestations, and stimulating chondriosomal bioenergetics. The current scrutiny is an effort to illuminate the neuroprotective action of NPs in various PD-experiencing models. The authors carried out a methodical inspection of the published work procured through reputable online portals like PubMed, MEDLINE, EMBASE, and Frontier, by employing specific keywords in the subject of our article. Additionally, the manuscript concentrates on representing the pathways concerned in bringing neuroprotective action of NPs in PD. In sum, NPs exert substantial neuroprotection through regulating paramount pathways indulged in PD advancement, and consequently, might be a newfangled and eloquent perspective in PD therapy.
帕金森病(PD)是一种严重、主要的神经细胞破坏性疾病,主要影响中脑区域的多巴胺能(DArgic)神经细胞,即黑质致密部(SN-PC)。尽管该疾病的确切病因尚不确定,但现有证据表明,衰老、遗传易感性和环境毒素对 PD 的进展有很大影响。此外,PD 进展中涉及的病理生理机制包括α-突触核蛋白在路易体(LB)和路易神经突中的聚集、氧化应激、细胞凋亡、神经元炎症以及线粒体、自噬溶酶体途径(ALP)和泛素-蛋白酶体系统(UPS)的异常运作。目前的治疗方法只能缓解 PD 相关症状,但到目前为止,还没有治疗候选药物被描述为能完全阻止疾病进展。神经肽(NPs)是一种小的、包含蛋白质的额外信使物质,通常由整个神经系统中的神经细胞产生和释放。许多 NPs,例如 P 物质(SP)、胃饥饿素、神经肽 Y(NPY)、神经降压素、垂体腺苷酸环化酶激活肽(PACAP)、nesfatin-1 和生长抑素,已被证明在体内和体外 PD 模型中具有重要的神经保护作用,通过抑制细胞凋亡、细胞毒性、氧化应激、炎症、自噬、神经元毒性、小胶质细胞刺激、减轻疾病相关症状和刺激线粒体生物能学。目前的研究旨在阐明 NPs 在各种 PD 模型中的神经保护作用。作者通过在 PubMed、MEDLINE、EMBASE 和 Frontier 等知名在线门户上使用我们文章主题的特定关键词,对已发表的文献进行了系统的检查。此外,本文还重点介绍了涉及 NPs 在 PD 中发挥神经保护作用的途径。总之,NPs 通过调节 PD 进展中涉及的重要途径发挥重要的神经保护作用,因此,可能是 PD 治疗的一个新的、有说服力的观点。