Sorbonne Université, F-75013, Paris, France; Inserm, U1127, F-75013 Paris, France; CNRS, UMR 7225, F-75013 Paris, France; Institut du Cerveau et de la Moelle Epinière, ICM, F-75013 Paris, France.
Sorbonne Université, F-75013, Paris, France; Inserm, U1127, F-75013 Paris, France; CNRS, UMR 7225, F-75013 Paris, France; Institut du Cerveau et de la Moelle Epinière, ICM, F-75013 Paris, France; PSL Research University, Ecole Pratique des Hautes Etudes, Laboratoire de Neurogénétique, F-75013 Paris, France.
J Mol Biol. 2020 Apr 3;432(8):2714-2734. doi: 10.1016/j.jmb.2020.02.033. Epub 2020 Mar 5.
Rare genetic diseases affect a limited number of patients, but their etiology is often known, facilitating the development of reliable animal models and giving the opportunity to investigate physiopathology. Lysosomal storage disorders are a group of rare diseases due to primary alteration of lysosome function. These diseases are often associated with neurological symptoms, which highlighted the importance of lysosome in neurodegeneration. Likewise, other groups of rare neurodegenerative diseases also present lysosomal alteration. Lysosomes fuse with autophagosomes and endosomes to allow the degradation of their content thanks to hydrolytic enzymes. It has emerged that alteration of the autophagy-lysosome pathway could play a critical role in neuronal death in many neurodegenerative diseases. Using a repertoire of selected rare neurodegenerative diseases, we highlight that a variety of alterations of the autophagy-lysosome pathway are associated with neuronal death. Yet, in most cases, it is still unclear why alteration of this pathway can lead to neurodegeneration.
罕见遗传病通常影响少数患者，但由于其病因通常已知，因此有助于开发可靠的动物模型，并提供研究病理生理学的机会。溶酶体贮积症是一组由于溶酶体功能原发性改变而导致的罕见疾病。这些疾病常伴有神经症状，这凸显了溶酶体在神经退行性变中的重要性。同样，其他组罕见的神经退行性疾病也存在溶酶体改变。溶酶体与自噬体和内体融合，使其中的内容物通过水解酶降解。现在已经发现，自噬溶酶体途径的改变可能在许多神经退行性疾病中的神经元死亡中起关键作用。使用一组选定的罕见神经退行性疾病，我们强调多种自噬溶酶体途径的改变与神经元死亡有关。然而，在大多数情况下，仍不清楚为什么该途径的改变会导致神经退行性变。
