Oizumi Hideki, Yamasaki Kenshi, Suzuki Hiroyoshi, Hasegawa Takafumi, Sugimura Yoko, Baba Toru, Fukunaga Kohji, Takeda Atsushi
Department of Neurology, National Hospital Organization, Sendai Nishitaga Hospital, Sendai, Japan.
Department of Dermatology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Front Aging Neurosci. 2021 Mar 25;13:648982. doi: 10.3389/fnagi.2021.648982. eCollection 2021.
Parkinson's disease (PD) and multiple system atrophy are types of adult-onset neurodegenerative disorders named synucleinopathies, which are characterized by prominent intracellular α-synuclein (αSyn) aggregates. We have previously found that αSyn aggregates and the vulnerability of dopaminergic neurons in the mouse brain are partly associated with the expression of fatty acid-binding protein 3 (FABP3, heart FABP). However, it remains to be elucidated whether FABP3 accumulation is associated with αSyn aggregates in human tissues. Here, we histologically studied FABP3 expression in human tissues obtained from patients with synucleinopathies, patients with Alzheimer disease (AD) and controls. We found that (1) a variety of neurons expressed the FABP3 protein in human brain tissues, (2) FABP3 was colocalized with αSyn aggregates in the brains of individuals with synucleinopathies but not with amyloid β or p-tau aggregates in the brains of individuals with AD, and (3) FABP3 was not present in p-αSyn deposits in biopsied skin tissues from individuals with PD. These findings suggest that FABP3 expression is associated with αSyn aggregation in synucleinopathies and provide new insights into the involvement of FABP3 in synucleinopathies.
帕金森病(PD)和多系统萎缩是成人起病的神经退行性疾病,属于突触核蛋白病,其特征是细胞内出现显著的α-突触核蛋白(αSyn)聚集体。我们之前发现,小鼠脑中的αSyn聚集体和多巴胺能神经元的易损性与脂肪酸结合蛋白3(FABP3,心脏型FABP)的表达部分相关。然而,FABP3的积累是否与人体组织中的αSyn聚集体相关仍有待阐明。在此,我们对取自突触核蛋白病患者、阿尔茨海默病(AD)患者及对照的人体组织中的FABP3表达进行了组织学研究。我们发现:(1)多种神经元在人脑组织中表达FABP3蛋白;(2)在突触核蛋白病患者的大脑中,FABP3与αSyn聚集体共定位,但在AD患者大脑中不与淀粉样β蛋白或磷酸化tau蛋白聚集体共定位;(3)在PD患者的活检皮肤组织中,p-αSyn沉积物中不存在FABP3。这些发现表明,FABP3表达与突触核蛋白病中的αSyn聚集相关,并为FABP3在突触核蛋白病中的作用提供了新见解。