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Promoting Endogenous Neurogenesis as a Treatment for Alzheimer’s Disease

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Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is the most universal neurodegenerative disorder characterized by memory loss and cognitive impairment. AD is biologically defined by production and aggregation of misfolded protein including extracellular amyloid β (Aβ) peptide and intracellular microtubule-associated protein tau tangles in neurons, leading to irreversible neuronal loss. At present, regulation of endogenous neurogenesis to supplement lost neurons has been proposed as a promising strategy for treatment of AD. However, the exact underlying mechanisms of impaired neurogenesis in AD have not been fully explained and effective treatments targeting neurogenesis for AD are limited. In this review, we mainly focus on the latest research of impaired neurogenesis in AD. Then we discuss the factors affecting stages of neurogenesis and the interplay between neural stem cells (NSCs) and neurogenic niche under AD pathological conditions. This review aims to explore potential therapeutic strategies that promote endogenous neurogenesis for AD treatments.

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Abbreviations

AD:

Alzheimer’s disease

AHN:

Adult hippocampal neurogenesis

aNSCs:

Activated neural stem cells

APP:

Amyloid precursor protein

Aβ:

Amyloid β

BDNF:

Brain-derived neurotrophic factor

bHLH:

Basic helix-loop-helix

BMP:

Bone morphogenetic protein

BLBP:

Brain lipid-binding protein

CCK:

Cholecystokinin

CDK:

Cyclin-dependent kinase

DCX:

Doublecortin X

DG:

Dentate gyrus

Ebd1:

Earthbound1/jerky

EE:

Environmental enrichment

GABA:

γ-Aminobutyric acid

Gadd45γ:

Growth arrest and DNA damage 45 gamma

GC:

Granule cells

GCL:

Granule cell layer

GFAP:

Glial fibrillary acidic protein

IGF-1:

Insulin-like growth factor 1

Klf9:

Kruppel-like factor 9

MC:

Mossy cells

MCT1:

Monocarboxylic acid transporter 1

MFGE8:

Milk fat globule-epidermal growth factor (EGF) 8

mGluR5:

Metabotropic glutamate receptor subtype 5

MOL:

Molecular layer

NGF:

Nerve growth factor

Ngn2:

Neurogenin2

NMDA:

N-Methyl-d-aspartate

NPC:

Neural progenitor cells

NSCs:

Neural stem cells

NT-3:

Neurotrophin-3

PV:

Parvalbumin

qNSCs:

Quiescent neural stem cells

REST:

RE-1 silencing transcription factor

SGZ:

Subgranular zone

SOX2:

Sry-related HMG box transcription factor 2

SST:

Somatostatin

TLR4:

Toll-like receptor 4

VEGF:

Vascular endothelial growth factor

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This review was supported by funding from Science and Technology Development Planning Program of Jilin Province (20190304029YY), Changchun Science and Technology Planning Project (21ZY18).

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  1. Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin Province, China

    Qiang Zhang, Jingyue Liu, Li Chen & Ming Zhang

  2. School of Nursing, Jilin University, Changchun, China

    Li Chen

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Zhang, Q., Liu, J., Chen, L. et al. Promoting Endogenous Neurogenesis as a Treatment for Alzheimer’s Disease. Mol Neurobiol 60, 1353–1368 (2023). https://doi.org/10.1007/s12035-022-03145-2

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