scholarly journals Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuan-Yuan Xie ◽  
Ting-Ting Pan ◽  
De-en Xu ◽  
Xin Huang ◽  
Yong Tang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Short Term Memory ◽  
Therapeutic Potential ◽  
Disease Model ◽  
Model Mouse ◽  
Oligodendrocyte Precursor ◽  
Myelin Deficits ◽  
M1 Muscarinic

Disrupted myelin and impaired myelin repair have been observed in the brains of patients and various mouse models of Alzheimer’s disease (AD). Clemastine, an H1-antihistamine, shows the capability to induce oligodendrocyte precursor cell (OPC) differentiation and myelin formation under different neuropathological conditions featuring demyelination via the antagonism of M1 muscarinic receptor. In this study, we investigated if aged APPSwe/PS1dE9 mice, a model of AD, can benefit from chronic clemastine treatment. We found the treatment reduced brain amyloid-beta deposition and rescued the short-term memory deficit of the mice. The densities of OPCs, oligodendrocytes, and myelin were enhanced upon the treatment, whereas the levels of degraded MBP were reduced, a marker for degenerated myelin. In addition, we also suggest the role of clemastine in preventing OPCs from entering the state of cellular senescence, which was shown recently as an essential causal factor in AD pathogenesis. Thus, clemastine exhibits therapeutic potential in AD via preventing senescence of OPCs.

scholarly journals Role of TREM2 deficiency in Alzheimer’s disease model mice expressing human APOE3 or APOE4

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Nicholas F. Fitz ◽  
Kyong Nyon Nam ◽  
Florent Letronne ◽  
Cody M. Wolfe ◽  
Brittany E. Playso ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Model ◽  
Human Apoe3

P1-089: ADMINISTRATION OF BIFIDOBACTERIUM BREV E STRAIN A1 PREVENTS COGNITIVE IMPAIRMENT IN AN ALZHEIMER'S DISEASE MODEL MOUSE

2006 ◽  
Vol 14 (7S_Part_5) ◽  
pp. P305-P305
Author(s):  
Yodai Kobayashi ◽  
Kousuke Shimada ◽  
Eri Mitsuyama ◽  
Tetsuya Kuhara ◽  
Akihito Yasuoka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Disease Model ◽  
Model Mouse

scholarly journals Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer’s disease mice

2022 ◽  
Vol 119 (3) ◽  
pp. e2115082119
Author(s):  
Min Hee Park ◽  
Kang Ho Park ◽  
Byung Jo Choi ◽  
Wan Hui Han ◽  
Hee Ji Yoon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Memory Function ◽  
Selective Inhibition ◽  
Acid Sphingomyelinase ◽  
Hippocampal Neurogenesis ◽  
Ghrelin Receptor ◽  
Dual Action

Alzheimer’s disease (AD) is characterized by complex, multifactorial neuropathology, suggesting that small molecules targeting multiple neuropathological factors are likely required to successfully impact clinical progression. Acid sphingomyelinase (ASM) activation has been recognized as an important contributor to these neuropathological features in AD, leading to the concept of using ASM inhibitors for the treatment of this disorder. Here we report the identification of KARI 201, a direct ASM inhibitor evaluated for AD treatment. KARI 201 exhibits highly selective inhibition effects on ASM, with excellent pharmacokinetic properties, especially with regard to brain distribution. Unexpectedly, we found another role of KARI 201 as a ghrelin receptor agonist, which also has therapeutic potential for AD treatment. This dual role of KARI 201 in neurons efficiently rescued neuropathological features in AD mice, including amyloid beta deposition, autophagy dysfunction, neuroinflammation, synaptic loss, and decreased hippocampal neurogenesis and synaptic plasticity, leading to an improvement in memory function. Our data highlight the possibility of potential clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.

scholarly journals Protective role of caffeic acid in an Aβ25-35-induced Alzheimer's disease model

2015 ◽  
Vol 9 (5) ◽  
pp. 480 ◽  
Author(s):  
Ji Hyun Kim ◽  
Qian Wang ◽  
Ji Myung Choi ◽  
Sanghyun Lee ◽  
Eun Ju Cho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Caffeic Acid ◽  
Disease Model ◽  
Protective Role

scholarly journals Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer's disease model mouse

2011 ◽  
Vol 6 (1) ◽  
pp. 20 ◽  
Author(s):  
Ayumi Takamura ◽  
Yasuhide Okamoto ◽  
Takeshi Kawarabayashi ◽  
Tatsuki Yokoseki ◽  
Masao Shibata ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Basis ◽  
Disease Model ◽  
Memory Loss ◽  
Model Mouse

scholarly journals Essential roles of plexin-B3+ oligodendrocyte precursor cells in the pathogenesis of Alzheimer’s disease

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Naomi Nihonmatsu-Kikuchi ◽  
Xiu-Jun Yu ◽  
Yoshiki Matsuda ◽  
Nobuyuki Ozawa ◽  
Taeko Ito ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Culture Method ◽  
Defined Medium ◽  
Fibroblast Growth Factor 2 ◽  
Oligodendrocyte Progenitor Cells ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Oligodendrocyte Precursor

AbstractThe role of oligodendrocyte lineage cells, the largest glial population in the adult central nervous system (CNS), in the pathogenesis of Alzheimer’s disease (AD) remains elusive. Here, we developed a culture method for adult oligodendrocyte progenitor cells (aOPCs). Fibroblast growth factor 2 (FGF2) promotes survival and proliferation of NG2+ aOPCs in a serum-free defined medium; a subpopulation (~5%) of plexin-B3+ aOPCs was also found. FGF2 withdrawal decreased NG2+, but increased plexin-B3+ aOPCs and Aβ1-42 secretion. Plexin-B3+ aOPCs were distributed throughout the adult rat brain, although less densely than NG2+ aOPCs. Spreading depolarization induced delayed cortical plexin-B3+ aOPC gliosis in the ipsilateral remote cortex. Furthermore, extracellular Aβ1-42 accumulation was occasionally found around plexin-B3+ aOPCs near the lesions. In AD brains, virtually all cortical SPs were immunostained for plexin-B3, and plexin-B3 levels increased significantly in the Sarkosyl-soluble fractions. These findings suggest that plexin-B3+ aOPCs may play essential roles in AD pathogenesis, as natural Aβ-secreting cells.

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