Diabetes-induced Central Neuritic Dystrophy and Cognitive Deficits Are Associated with the Formation of Oligomeric Reticulon-3 via Oxidative Stress

Zhao, Baosheng; Pan, Bai Shen; Shen, Su; Sun, Xiao; Hou, Zheng Zhou; Yan, Riqiang; Sun, Feng

doi:10.1074/jbc.m112.440784

Cited by 37 publications

(23 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another possibility is the “toxic” effect of hyperglycemia which can lead to progressive structural and functional abnormalities in the brain [58]. Such glucose toxicity is mediated by increased flux of glucose through the polyol and hexosamine pathway [59], increased productions of oxidative stress [60], and accumulations of advanced glycation end-products [61]. Nevertheless, the present study may provide some clues for the role that hyperglycemia could have played in the pathogenesis of cerebral dysfunction at the early stage of T2DM.…”

Section: Discussionmentioning

confidence: 99%

Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics

Wang

Zhu

et al. 2014

Acta Diabetol

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is well known for its adverse impacts on brain and cognition, which lead to multidimensional cognitive deficits and wildly-spread cerebral structure abnormalities. However, existing literatures are mainly focused on patients with advanced age or extended T2DM duration. Therefore, it remains unclear whether and how brain function would be affected at the initial onset stage of T2DM in relatively younger population. In current study, twelve newly-diagnosed middle-aged T2DM patients with no previous diabetic treatment history and twelve matched controls were recruited. Brain activations during a working memory task, the digit n-back paradigm (0-, 1- and 2-back), were obtained with functional magnetic resonance imaging (fMRI) and tested by repeated measures ANOVA. Whereas patients performed the n-back task comparably well as controls, significant load-by-group interactions of brain activation were found in the right dorsolateral prefrontal cortex (DLPFC), left middle/inferior frontal gyrus, and left parietal cortex, where patients exhibited hyperactivation in the 2-back but not the 0-back or 1-back condition compared to controls. Furthermore, the severity of chronic hyperglycemia, estimated by glycosylated hemoglobin (HbA1c) level, was entered into partial correlational analyses with task-related brain activations, while controlling for the real-time influence of glucose, estimated by instant plasma glucose level measured before scanning. Significant positive correlations were found between HbA1c and brain activations in the anterior cingulate cortex and bilateral DLPFC only in patients. Taken together, these findings suggest there might be a compensatory mechanism due to brain inefficiency related to chronic hyperglycemia at the initial onset stage of T2DM.

show abstract

Section: Discussionmentioning

confidence: 99%

Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics

Wang

Zhu

et al. 2014

Acta Diabetol

View full text Add to dashboard Cite

show abstract

“…As typical AD (plaques and tangles) and PD (Lewy body and neurites) pathologies may coexist in clinically diagnosed AD or PD patients (or aged individuals) [125], the possibility of α-synuclein colocalization with AβPP or BACE1 in dystrophic neurites is worth further investigation. For additional examples, evidence suggests that axonal or neuritic pathology is associated with ischemic cerebral stroke [112, 113] and diabetic neuropathy [126]. …”

Section: Introductionmentioning

confidence: 99%

Can BACE1 Inhibition Mitigate Early Axonal Pathology in Neurological Diseases?

Xiao

Gai

et al. 2013

JAD

View full text Add to dashboard Cite

β-Secretase-1 (BACE1) is the rate-limiting enzyme for the genesis of amyloid-β (Aβ) peptides, the main constituents of the amyloid plaques in the brains of Alzheimer’s disease (AD) patients. BACE1 is being evaluated as an anti-Aβ target for AD therapy. Recent studies indicate that BACE1 elevation is associated with axonal and presynaptic pathology during plaque development. Evidence also points to a biological role for BACE1 in axonal outgrowth and synapse formation during development. Axonal, including presynaptic, pathology exists in AD as well as many other neurological disorders such as Parkinson’s disease, epilepsy, stroke, and trauma. In this review, we discuss pharmaceutical BACE1 inhibition as a therapeutic option for axonal pathogenesis, in addition to amyloid pathology. We first introduce the amyloidogenic processing of amyloid-β protein precursor and describe the normal expression pattern of the amyloidogenic proteins in the brain, with an emphasis on BACE1. We then address BACE1 elevation relative to amyloid plaque development, followed by updating recent understanding of a neurotrophic role of BACE1 in axon and synapse development. We further elaborate the occurrence of axonal pathology in some other neurological conditions. Finally, we propose pharmacological inhibition of excessive BACE1 activity as an option to mitigate early axonal pathology occurring in AD and other neurological disorders.

show abstract

“…Increased expression of RTNs significantly reduces the production of A␤ in both cultured cells and transgenic mouse models (23,(35)(36)(37)(38). This reduction is due to at least two effects.…”

mentioning

confidence: 99%

Increased Expression of Reticulon 3 in Neurons Leads to Reduced Axonal Transport of β Site Amyloid Precursor Protein-cleaving Enzyme 1

Deng

Tan

et al. 2013

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Axonal transport of BACE1 and the regulation of BACE1 synaptic localization remain to be fully characterized. Results: Colocalization of BACE1 with synaptophysin was reduced by overexpression of RTN3. This reduction was due to reduced BACE1 axonal transport. Conclusion: Increased interaction of RTN3 with BACE1 in the soma impacts axonal transport of BACE1. Significance: Changes of BACE1 synaptic localization potentially alter synaptic A␤ generation and amyloid deposition.

show abstract

Diabetes-induced Central Neuritic Dystrophy and Cognitive Deficits Are Associated with the Formation of Oligomeric Reticulon-3 via Oxidative Stress

Cited by 37 publications

References 56 publications

Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics

Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics

Can BACE1 Inhibition Mitigate Early Axonal Pathology in Neurological Diseases?

Increased Expression of Reticulon 3 in Neurons Leads to Reduced Axonal Transport of β Site Amyloid Precursor Protein-cleaving Enzyme 1

Contact Info

Product

Resources

About