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作 者:Julia Chocarro JoséL.Lanciego
机构地区:[1]CNS Gene Therapy Department,Center for Applied Medical Research(CIMA),University of Navarra,Pamplona,Spain [2]Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CiberNed-ISCⅢ),Madrid,Spain [3]Aligning Science Across Parkinson’s(ASAP)Collaborative Research Network,Chevy Chase,MD,USA
出 处:《Neural Regeneration Research》2026年第1期224-232,共9页中国神经再生研究(英文版)
基 金:supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033;FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research;by CiberNed Intramural Collaborative Projects(ref.PI2020/09);by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
摘 要:The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
关 键 词:adeno-associated viral vectors ALPHA-SYNUCLEIN DOPAMINE Lewy bodies NEURODEGENERATION NEUROMELANIN NEUROPATHOLOGY substantia nigra
分 类 号:R74[医药卫生—神经病学与精神病学]
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