Raj Aiswarya, Bandyopadhyay Urmi
Manipal Institute of Regenerative Medicine (MIRM), Bengaluru, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India.
Front Neurosci. 2024 Jan 8;17:1331211. doi: 10.3389/fnins.2023.1331211. eCollection 2023.
Lysosomes primarily recognized as center for cellular 'garbage-disposing-unit', which has recently emerged as a crucial regulator of cellular metabolism. This organelle is a well-known vital player in the pathology including neurodegenerative disorders. In pathological context, removal of intracellular damaged misfolded proteins, organelles and aggregates are ensured by 'Autophagy' pathway, which initially recognizes, engulfs and seals the toxic cargo at the cytosolic environment. Thereafter the cell completes the task of encapsulated cargo elimination upon delivery of them to the terminal compartment - lysosome, which contains acid hydrolases, that are capable of degrading the abnormal protein-lipid-repertoire. The merge between inseparable 'Autophagy' and 'Lysosomal' pathways evolved into 'Autophagy-Lysosome Pathway (ALP)', through which cell ultimately degrades and recycles bio-materials for metabolic needs. Dysregulation of any of the steps of the multi-step ALP can contribute to the development and progression of disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Therefore, targeting differential steps of ALP or directly lysosomes using nano-bioengineering approaches holds great promise for therapeutic interventions. This review aims to explore the role of distal autophagy pathway and proximal lysosomal function, as cellular degradative and metabolic hubs, in healing neurological disorders and highlights the contributions of nano-bioengineering in this field. Despite multiple challenges, this review underscores the immense potential of integrating autophagy-lysosomal biology with nano-bioengineering to revolutionize the field and provide novel therapeutic avenues for tackling neurological-neurodegenerative-disorders.
溶酶体主要被认为是细胞的“垃圾处理单元”中心,最近它已成为细胞代谢的关键调节因子。这个细胞器在包括神经退行性疾病在内的病理学中是一个众所周知的重要角色。在病理情况下,细胞内受损的错误折叠蛋白、细胞器和聚集体的清除是通过“自噬”途径来确保的,该途径最初在细胞溶质环境中识别、吞噬并封存有毒物质。此后,细胞在将这些物质输送到终末区室——溶酶体后,完成对包裹物质的清除任务,溶酶体含有酸性水解酶,能够降解异常的蛋白质-脂质成分。不可分割的“自噬”和“溶酶体”途径之间的融合演变成了“自噬-溶酶体途径(ALP)”,通过该途径,细胞最终降解并回收生物材料以满足代谢需求。多步骤ALP的任何一个步骤失调都可能导致包括阿尔茨海默病(AD)、帕金森病(PD)和亨廷顿病(HD)在内的疾病的发生和发展。因此,使用纳米生物工程方法靶向ALP的不同步骤或直接靶向溶酶体在治疗干预方面具有巨大潜力。本综述旨在探讨远端自噬途径和近端溶酶体功能作为细胞降解和代谢中心在治愈神经系统疾病中的作用,并强调纳米生物工程在该领域的贡献。尽管存在多重挑战,但本综述强调了将自噬-溶酶体生物学与纳米生物工程相结合以彻底改变该领域并为解决神经-神经退行性疾病提供新治疗途径的巨大潜力。
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