Ginsenoside Rd Attenuates Tau Phosphorylation in Olfactory Bulb, Spinal Cord, and Telencephalon by Regulating Glycogen Synthase Kinase 3β and Cyclin-Dependent Kinase 5.

Ling Li,Tian Li,Xin Tian,Ling Zhao,Weidong Pan

doi:10.1155/2021/4485957

Abstract

Objective Ginseng is a plant of the family Acanthopanaceae. It has been used for thousands of years in China. It is known as the king of hundred herbs. It was recorded first in Shennong Baicao Jing. It has been found that ginsenoside Rd is a neuroprotective agent. This article aims to explore the protective roles of ginsenoside Rd in Alzheimer's disease. Rd, a Chinese herb, may be a promising treatment drug for Alzheimer′s disease (AD) and is also reported to be related to several pathological changes, including the deposition of Aβ and tau hyperphosphorylation in AD as it decreases the deposition of tau hyperphosphorylation in APP transgenic mice. Methods In this study, APP transgenic mice were pretreated with 10 mg/kg Rd for six months, and the effect of Rd on neuropathological deficits in the olfactory bulb, spinal cord, and telencephalon of APP transgenic mice was investigated. The phosphorylation levels of tau (S199/202, S396, S404, and Tau5) and the activities of the proteins glycogen synthase kinase 3β (Tyr216) and cyclin-dependent kinase 5 (P25/P35) were measured. Results The pretreatment of Rd effectively decreased the production and deposition of hyperphosphorylated tau (S199/202, S396, and S404) protein by depressing the expression of glycogen synthase kinase 3β (GSK-3β/Tyr216) and cyclin-dependent kinase 5 (CDK5/P25). Conclusion These findings suggest that ginsenoside Rd could improve the pathological changes of AD in the olfactory bulb, spinal cord, and telencephalon, which further demonstrated the potential therapeutic effect of Rd in early AD.

Highlights

Alzheimer’s disease (AD) is an age-related neurodegenerative disease with clinical manifestations of cognitive impairment and sensory and motor loss
Studies have shown that olfactory impairment is a major part of cognitive impairment in AD, and olfactory impairment is highly correlated with Aβ deposition and tau hyperphosphorylation [7], especially olfactory bulb (OB) [25], which occurs outside the cortex and hippocampus
OB is the first site of brain olfactory information processing, and its disorder is related to AD

Summary

Introduction

Alzheimer’s disease (AD) is an age-related neurodegenerative disease with clinical manifestations of cognitive impairment and sensory and motor loss. Its pathological manifestations include amyloid beta-senile plaque, nerve fiber tangles, and neuroinflammatory response. Most studies [1] about AD focus on the hippocampus, which is considered to be the main area of cognitive memory. Little attention has been paid to other areas of the central nervous system (CNS), such as the olfactory bulb (OB), spinal cord (SP), and telencephalon (CE). Studies have shown that betaamyloid plaques [2], nerve fiber tangles, and hyperphosphorylated tau [3] can accumulate in the spinal cord and telencephalon of AD patients. E decline of olfactory function is a part of the clinical phenotype of neurodegenerative diseases including AD. As a cortical sensory structure, the olfactory bulb (OB) is the first synaptic relay station for olfactory perception in the brain, which receives input directly from olfactory neurons in the nasal

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Conclusion