Epigenetic Control of CDK5 Promoter Regulates Diabetes-Associated Development of Alzheimer’s Disease

Autor: Zhen-Zhen Fan, Ting Tian, Chon-Chon Zhao, Zhao-Ming Ge, Hong-Bin Cai
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Tau protein
Morris water navigation task
Hyperphosphorylation
tau Proteins
Diet
High-Fat
Methylation
Epigenesis
Genetic
Diabetes Complications
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Alzheimer Disease
Internal medicine
Glucose Intolerance
medicine
Animals
Epigenetics
Phosphorylation
Maze Learning
Promoter Regions
Genetic
CA1 Region
Hippocampal
biology
General Neuroscience
Cyclin-dependent kinase 5
Neurodegeneration
Acetylation
Cyclin-Dependent Kinase 5
Recognition
Psychology
General Medicine
medicine.disease
Rats
Psychiatry and Mental health
Clinical Psychology
Glucose
030104 developmental biology
Endocrinology
nervous system
biology.protein
Insulin Resistance
Geriatrics and Gerontology
030217 neurology & neurosurgery
Zdroj: Journal of Alzheimer's Disease. 69:743-750
ISSN: 1875-8908
1387-2877
DOI: 10.3233/jad-190227
Popis: Cyclin-dependent kinase-5 (CDK5) is activated by p35 and then binds to both p35 and its truncated form p25 to promote hyperphosphorylation of tau protein, thereby facilitating the pathological progression of Alzheimer's disease (AD). However, it is unknown whether a patient's diabetic status promotes the later onset of AD in a CDK5-dependent manner. Here, we induced pro-diabetic insulin resistance and glucose intolerance in rats using a combined high fat and high glucose diet. Compared to normal diet-fed rats, these pro-diabetic rats exhibited poorer behavioral performance in the Morris water maze test and the novel object recognition test. Increased phosphorylation of tau protein was detected in the hippocampal CA1 region of the rat brain, suggesting neurodegeneration. Moreover, CDK5 transcriptional activity was significantly increased in the HFGD-rat brain, likely resulting from an increase in acetylation and a decrease in methylation of the CDK5 promoter. Together, these data suggest that epigenetic control of the CDK5 promoter by acetylation and methylation may regulate the diabetes-associated development of AD.
Databáze: OpenAIRE
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