Distribution of SLC10A4, a Synaptic Vesicle Protein in the Human Brain, and the Association of this Protein with Alzheimer's Disease-Related Neuronal Degeneration

2013 ◽  
Vol 37 (3) ◽  
pp. 603-610 ◽  
Author(s):  
Svetlana N. Popova ◽  
Irina Alafuzoff
2011 ◽  
Vol 7 ◽  
pp. S587-S587
Author(s):  
Suthicha Wuwongse ◽  
Clara Hiu-Ling Hung ◽  
Natalie Qishan Zhang ◽  
Yuen-Shan Ho ◽  
Raymond Chuen-Chung Chang ◽  
...  

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Annika Öhrfelt ◽  
Ann Brinkmalm ◽  
Julien Dumurgier ◽  
Gunnar Brinkmalm ◽  
Oskar Hansson ◽  
...  

Author(s):  
Yanyan Kong ◽  
Lin Huang ◽  
Weihao Li ◽  
Xuanting Liu ◽  
Yinping Zhou ◽  
...  

Alzheimer’s disease (AD), a serious neurodegenerative disease, is pathologically characterized by synaptic loss and dysfunction. Synaptic vesicle protein 2A (SV2A) is an indispensable vesicular protein specifically expressed in synapses and can be used as a biomarker for synaptic density. We found that the expression of SV2A was down-regulated in the hippocampus of AD patients, yet the relation of SV2A to other hallmarks of AD pathology such as amyloid precursor protein (APP), β-amyloid (Aβ), and Tau protein is not thoroughly clear. In addition, SV2A colocalized with APP and was down-regulated at Aβ deposition. Moreover, we found that SV2A deficiency leads to a simultaneous increase in Aβ and Tau hyperphosphorylation, while SV2A overexpression was associated with downregulation of β-site APP cleaving enzyme 1 and apolipoprotein E genes. In addition, evidence gained in the study points to the phosphatidylinositol 3-kinase signaling pathway as a possible mediator in SV2A regulation influencing the incidence and development of AD. With limited effective diagnostic methods for AD, a close interplay between SV2A and AD-related proteins demonstrated in our study may provide novel and innovative diagnostic and therapeutic opportunities.


2020 ◽  
Vol 16 (S4) ◽  
Author(s):  
Barbara B Bendlin ◽  
Alexandra H DiFilippo ◽  
Tobey J Betthauser ◽  
Nathaniel A Chin ◽  
Dhanabalan Murali ◽  
...  

Author(s):  
Zeba Firdaus ◽  
Tryambak Deo Singh

: Alzheimer’s disease (AD) is an age-associated nervous system disorder and a leading cause of dementia worldwide. Clinically it is described by cognitive impairment, and pathophysiologically by deposition of amyloid plaques and neurofibrillary tangles in the brain and neurodegeneration. This article reviews the pathophysiology, course of neuronal degeneration, and the various possible hypothesis of AD progression. These hypotheses include amyloid cascade, tau hyperphosphorylation, cholinergic disruption, metal dysregulation, vascular dysfunction, oxidative stress, and neuroinflammation. There is an exponential increase in the occurrence of the AD in recent few years that indicate an urgent need to develop some effective treatment. Currently, only 2 classes of drugs are available for AD treatment namely acetylcholinesterase inhibitor and NMDA receptor antagonist. Since AD is a complex neurological disorder and these drugs use a single target approach, alternatives are needed due to limited effectiveness and unpleasant side-effects of these drugs. Currently, plants have been used for drug development research especially because of their multiple sites of action and fewer side effects. Uses of some herbs and phytoconstituents for the management of neuronal disorders like AD have been documented in this article. Phytochemical screening of these plants shows the presence of many beneficial constituents like flavonoids, triterpenes, alkaloids, sterols, polyphenols, and tannins. These compounds show a wide array of pharmacological activities such as anti-amyloidogenic, anticholinesterase, and antioxidant. This article summarizes the present understanding of AD progression and gathers biochemical evidence from various works on natural products that can be useful in the management of this disease.


2021 ◽  
pp. 1-14
Author(s):  
Pan Liu ◽  
Qian Yang ◽  
Ning Yu ◽  
Yan Cao ◽  
Xue Wang ◽  
...  

Background: Alzheimer’s disease (AD) is one of the most challenging diseases causing an increasing burden worldwide. Although the neuropathologic diagnosis of AD has been established for many years, the metabolic changes in neuropathologic diagnosed AD samples have not been fully investigated. Objective: To elucidate the potential metabolism dysregulation in the postmortem human brain samples assessed by AD related pathological examination. Methods: We performed untargeted and targeted metabolomics in 44 postmortem human brain tissues. The metabolic differences in the hippocampus between AD group and control (NC) group were compared. Results: The results show that a pervasive metabolic dysregulation including phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis, biotin metabolism, and purine metabolism are associated with AD pathology. Targeted metabolomics reveal that phenylalanine, phenylpyruvic acid, and N-acetyl-L-phenylalanine are upregulated in AD samples. In addition, the enzyme IL-4I1 catalyzing transformation from phenylalanine to phenylpyruvic acid is also upregulated in AD samples. Conclusion: There is a pervasive metabolic dysregulation in hippocampus with AD-related pathological changes. Our study suggests that the dysregulation of phenylalanine metabolism in hippocampus may be an important pathogenesis for AD pathology formation.


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