Brain proteomics links oxidative stress with metabolic and cellular stress response proteins in behavioural alteration of Alzheimer's disease model rats.

Mohammad Azizur Rahman,Noorlidah Abdullah,Shahdat Hossain,Norhaniza Aminudin

doi:10.3934/neuroscience.2019.4.299

Mohammad Azizur Rahman, Noorlidah Abdullah + Show 2 more

Open Access

https://doi.org/10.3934/neuroscience.2019.4.299

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Abstract

Alzheimer's disease (AD) impairs memory and learning related behavioural performances of the affected person. Compared with the controls, memory and learning related behavioural performances of the AD model rats followed by hippocampal proteomics had been observed in the present study. In the eight armed radial maze, altered performance of the AD rats had been observed. Using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), 822 proteins had been identified with protein threshold at 95.0%, minimum peptide of 2 and peptide threshold at 0.1% FDR. Among them, 329 proteins were differentially expressed with statistical significance (P < 0.05). Among the significantly regulated (P < 0.05) 329 proteins, 289 met the criteria of fold change (LogFC of 1.5) cut off value. Number of proteins linked with AD, oxidative stress (OS) and hypercholesterolemia was 59, 20 and 12, respectively. Number of commonly expressed proteins was 361. The highest amount of proteins differentially expressed in the AD rats were those involved in metabolic processes followed by those linked with OS. Most notable was the perturbed state of the cholesterol metabolizing proteins in the AD group. Current findings suggest that proteins associated with oxidative stress, glucose and cholesterol metabolism and cellular stress response are among the mostly affected proteins in AD subjects. Thus, novel therapeutic approaches targeting these proteins could be strategized to withstand the ever increasing global AD burden.

Highlights

Alzheimer’s disease (AD) is the most common form of dementia, the deteriorated behavioural state that starts with gradual decrement of memory and learning capabilities
The rat was left untouched for a while so that adequate absorption could take place and sealed the pin holes with sterile bone foam and cement
Altered expression of different Heat shock proteins (HSPs) in the present study demonstrate their altered levels in the AD pathogenesis and corresponding amelioration in the respective subjects

Summary

Introduction

Alzheimer’s disease (AD) is the most common form of dementia, the deteriorated behavioural state that starts with gradual decrement of memory and learning capabilities. This occurs due to degeneration of the neurons associated with memory and learning in the hippocampus. AD patients face problem in remembering, recognizing, positioning and in executing personal activities. At advanced ages, they become solely dependent on their care-givers and family members. Contrary to the amyloid plaques, NFTs are intra-neuronal aggregates of misfolded and/or hyperphosphorylated tau protein. Synaptic and axonal degeneration result in cognitive impairment as well as dendritic atrophy, the retrograde degeneration of axons, and the eventual atrophy of dendrites and perikarya [1]

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