Department of Computational Biology, Indraprastha Institute of Information Technology (IIIT-Delhi) Okhla, Phase III, New Delhi, 110020, India.
Bioorganic Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) Jakkur P.O., Bengaluru, 560064, Karnataka, India.
Chembiochem. 2024 Jul 2;25(13):e202400224. doi: 10.1002/cbic.202400224. Epub 2024 Jun 14.
Neurodegenerative diseases (NDDs) refer to a complex heterogeneous group of diseases which are associated with the accumulation of amyloid fibrils or plaques in the brain leading to progressive loss of neuronal functions. Alzheimer's disease is one of the major NDD responsible for 60-80 % of all dementia cases. Currently, there are no curative or disease-reversing/modifying molecules for many of the NDDs except a few such as donepezil, rivastigmine, galantamine, carbidopa and levodopa which treat the disease-associated symptoms. Similarly, there are very few FDA-approved tracers such as flortaucipir (Tauvid) for tau fibril imaging and florbetaben (Neuraceq), flutemetamol (Vizamyl), and florbetapir (Amyvid) for amyloid imaging available for diagnosis. Recent advances in the cryogenic electron microscopy reported distinctly different microstructures for tau fibrils associated with different tauopathies highlighting the possibility to develop tauopathy-specific imaging agents and therapeutics. In addition, it is important to identify the proteins that are associated with disease development and progression to know about their 3D structure to develop various diagnostics, therapeutics and theranostic agents. The current article discusses in detail the disease-associated amyloid and non-amyloid proteins along with their structural insights. We comprehensively discussed various novel proteins associated with NDDs and their implications in disease pathology. In addition, we document various emerging chemical compounds developed for diagnosis and therapy of different NDDs with special emphasis on theranostic agents for better management of NDDs.
神经退行性疾病（NDDs）是一组复杂的异质性疾病，与大脑中淀粉样纤维或斑块的积累有关，导致神经元功能逐渐丧失。阿尔茨海默病是导致所有痴呆病例的 60-80%的主要 NDD 之一。目前，除了少数几种药物，如多奈哌齐、利伐斯的明、加兰他敏、卡比多巴和左旋多巴，可治疗与疾病相关的症状外，大多数 NDD 都没有治疗或疾病逆转/修饰的分子。同样，可用于诊断的经美国食品和药物管理局（FDA）批准的示踪剂也非常少，如用于 tau 纤维成像的 flortaucipir（Tauvid）和用于淀粉样成像的 florbetaben（Neuraceq）、flutemetamol（Vizamyl）和 florbetapir（Amyvid）。低温电子显微镜的最新进展报告称，与不同 tau 病相关的 tau 纤维具有明显不同的微观结构，这突出了开发 tau 病特异性成像剂和治疗剂的可能性。此外，确定与疾病发展和进展相关的蛋白质，了解其 3D 结构，对于开发各种诊断、治疗和治疗诊断试剂非常重要。本文详细讨论了与疾病相关的淀粉样和非淀粉样蛋白及其结构见解。我们全面讨论了与 NDD 相关的各种新型蛋白质及其在疾病病理学中的意义。此外，我们还记录了各种用于不同 NDD 诊断和治疗的新兴化学化合物，特别强调了治疗诊断试剂，以更好地管理 NDD。
