AMEM adult hippocampal neurogenesis and neuroregenerative therapy for Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia in the elderly
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Epidemiological data show that there are currently more than 48 million people suffering from AD worldwide
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However, there are currently no therapeutic drugs and methods that can stop the progression of AD
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Although the development of new drugs targeting the two pathological features of AD, namely abnormal accumulation of hyperphosphorylated tau protein (p-tau) in neurons and deposition of extracellular amyloid Aβ protein, has been in progress, most of them are in the final clinical trial stage due to Terminated due to poor efficacy
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Part of the reason may be related to the irreversibility of neural network degeneration in the brain of elderly AD patients
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Therefore, by inducing neuronal regeneration to compensate for neuronal loss and remodeling degenerated neuronal networks, it is expected to become a new direction for AD treatment
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Professor Zheng Jie from the Key Laboratory of Basic Pharmacology, Ministry of Education, Zunyi Medical University, reviewed the research progress of AD and hippocampal neurogenesis
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Figure 1: Hippocampal neurogenesis in adulthood
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(A) Schematic diagram of the anterior-posterior (ventral-dorsal) axis of the hippocampus
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(B) Biomarkers of AHN at different stages In different mammals, endogenous neuronal neogenesis has basically stopped after birth, and the dentate gyrus of the hippocampus is one of the few brain regions that retains neuronal neogenesis throughout life
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Although the number of (ie, adult hippocampalneurogenesis, AHN) is limited and susceptible to aging, disease and other factors, the small number of newborn neurons can still endow the hippocampal neural circuit with high plasticity, and in learning -Plays a vital role in the regulation of functions such as memory/forgetting and emotion
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This paper summarizes and analyzes the current researches on AHN changes in AD patients and rats/mice, pointing out that although there may be a transient increase in the number of hippocampal neurogenesis in the pre-middle stage of AD, the overall AHN (including stem cells and cells) may appear in the middle and late stages of AD.
division, differentiation of neural precursor cells and maturation of new neurons) were reduced
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Although endogenous AHN has great limitations in terms of quantity, scope, and types of new neurons, promoting AHN may still have certain significance for the prevention and treatment of AD
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At the same time, AHN can also be used as a simple, easy-to-obtain, stable and closest model to the actual brain conditions of AD patients to study and test other AD neuroregenerative treatment methods
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Figure 1: Comparison of gut microbial diversity between Chow group and DM group
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Figure 2: Summary diagram of potential neuroregenerative therapies In addition, this paper also reviews the research progress of inducing neurogenesis in AD brain by cell transplantation and inducing glial reprogramming, and analyzes its role in compensating for neuronal loss and remodeling.
There is a broad prospect in the treatment of Alzheimer's disease by altering neuronal networks, and there are still many problems and possible research directions in terms of the efficiency, specificity and safety of inducing neurogenesis
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Cite this paper: Zheng, J.
Hippocampal neurogenesis and pro-neurogenic therapies for Alzheimer's disease.
Anim Models Exp Med.
2022; 5: 3– 14.
doi:10.
1002/ame2.
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