Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, São Paulo, SP 05508-000, Brazil.
Departamento de Neurologia e Neurociências, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, São Paulo, SP 04039-032, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan 3;80(Pt A):34-53. doi: 10.1016/j.pnpbp.2017.04.033. Epub 2017 May 3.
Neuropsychiatric disorders involve various pathological mechanisms, resulting in neurodegeneration and brain atrophy. Neurodevelopmental processes have shown to be critical for the progression of those disorders, which are based on genetic and epigenetic mechanisms as well as on extrinsic factors. We review here common mechanisms underlying the comorbidity of Bipolar Disorders and Alzheimer's Disease, such as aberrant neurogenesis and neurotoxicity, reporting current therapeutic approaches. The understanding of these mechanisms precedes stem cell-based strategies as a new therapeutic possibility for treatment and prevention of Bipolar and Alzheimer's Disease progression. Taking into account the difficulty of studying the molecular basis of disease progression directly in patients, we also discuss the importance of stem cells for effective drug screening, modeling and treating psychiatric diseases, once in vitro differentiation of patient-induced pluripotent stem cells provides relevant information about embryonic origins, intracellular pathways and molecular mechanisms.
神经精神疾病涉及多种病理机制，导致神经退行性变和脑萎缩。神经发育过程已被证明对这些疾病的进展至关重要，这些疾病基于遗传和表观遗传机制以及外在因素。我们在这里回顾了双相情感障碍和阿尔茨海默病共病的常见机制，例如异常的神经发生和神经毒性，并报告了当前的治疗方法。这些机制的理解先于基于干细胞的策略，作为治疗和预防双相情感障碍和阿尔茨海默病进展的新治疗可能性。考虑到直接在患者中研究疾病进展的分子基础的困难，我们还讨论了干细胞在有效药物筛选、疾病建模和治疗中的重要性，因为患者诱导的多能干细胞的体外分化提供了关于胚胎起源、细胞内途径和分子机制的相关信息。
