Park_2020_Int.J.Mol.Sci_21_

Reference

Title : Human Neural Stem Cells Encoding ChAT Gene Restore Cognitive Function via Acetylcholine Synthesis, Abeta Elimination, and Neuroregeneration in APPswe\/PS1dE9 Mice - Park_2020_Int.J.Mol.Sci_21_
Author(s) : Park D , Choi EK , Cho TH , Joo SS , Kim YB
Ref : Int J Mol Sci , 21 : , 2020
Abstract :

In Alzheimer disease (AD) patients, degeneration of the cholinergic system utilizing acetylcholine for memory acquisition is observed. Since AD therapy using acetylcholinesterase (AChE) inhibitors are only palliative for memory deficits without slowing or reversing disease progress, there is a need for effective therapies, and stem cell-based therapeutic approaches targeting AD should fulfill this requirement. We established a human neural stem cell (NSC) line encoding choline acetyltransferase (ChAT) gene, an acetylcholine-synthesizing enzyme. APPswe/PS1dE9 AD model mice transplanted with the F3.ChAT NSCs exhibited improved cognitive function and physical activity. Transplanted F3.ChAT NSCs in the AD mice differentiated into neurons and astrocytes, produced ChAT protein, increased the ACh level, and improved the learning and memory function. F3.ChAT cell transplantation reduced Abeta deposits by recovering microglial function; i.e., the down-regulation of beta-secretase and inflammatory cytokines and up-regulation of Abeta-degrading enzyme neprilysin. F3.ChAT cells restored growth factors (GFs) and neurotrophic factors (NFs), and they induced the proliferation of NSCs in the host brain. These findings indicate that NSCs overexpressing ChAT can ameliorate complex cognitive and physical deficits of AD animals by releasing ACh, reducing Abeta deposit, and promoting neuroregeneration by the production of GFs/NFs. It is suggested that NSCs overexpressing ChAT could be a candidate for cell therapy in advanced AD therapy.

PubMedSearch : Park_2020_Int.J.Mol.Sci_21_
PubMedID: 32486466

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Citations formats

Park D, Choi EK, Cho TH, Joo SS, Kim YB (2020)
Human Neural Stem Cells Encoding ChAT Gene Restore Cognitive Function via Acetylcholine Synthesis, Abeta Elimination, and Neuroregeneration in APPswe\/PS1dE9 Mice
Int J Mol Sci 21 :

Park D, Choi EK, Cho TH, Joo SS, Kim YB (2020)
Int J Mol Sci 21 :