Aβ exacerbates α‐synuclein‐induced neurotoxicity through impaired insulin signaling in α‐synuclein‐overexpressed human SK‐N‐MC neuronal cells

Chang, Ching-Chi; Li, Hsin‐Hua; Chang, Yen-Ting; Ho, Ying-Jui; Hsieh, Ling-Jia; Chiu, Pai-Yi; Cheng, Yu-Shih; Lin, Chih‐Li; Lai, Te-Jen

doi:10.1111/cns.12772

Cited by 8 publications

(6 citation statements)

References 39 publications

(64 reference statements)

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“…In cultured neurons, exposure to exogenous Aβ increases synuclein aggregation via a reduction in autophagy (Lin et al, 2016a ). Aβ has been shown to affect autophagy through lowered AMPK activation and impaired insulin sensitivity (Park et al, 2012 ; Lin et al, 2016a ; Seixas da Silva et al, 2017 ; Chang et al, 2018 ). Tau fragments can block chaperone-mediated autophagy through incomplete entry into the lysosome.…”

Section: Sex and Autophagy Disruption In Alzheimer's Diseasementioning

confidence: 99%

Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease

Congdon

2018

Front. Neurosci.

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Alzheimer's disease (AD) is the most common form of dementia, with over 5. 4 million cases in the US alone (Alzheimer's Association, 2016). Clinically, AD is defined by the presence of plaques composed of Aβ and neurofibrillary pathology composed of the microtubule associated protein tau. Another key feature is the dysregulation of autophagy at key steps in the pathway. In AD, disrupted autophagy contributes to disease progression through the failure to clear pathological protein aggregates, insulin resistance, and its role in the synthesis of Aβ. Like many psychiatric and neurodegenerative diseases, the risk of developing AD, and disease course are dependent on the sex of the patient. One potential mechanism through which these differences occur, is the effects of sex hormones on autophagy. In women, the loss of hormones with menopause presents both a risk factor for developing AD, and an obvious example of where sex differences in AD can stem from. However, because AD pathology can begin decades before menopause, this does not provide the full answer. We propose that sex-based differences in autophagy regulation during the lifespan contribute to the increased risk of AD, and greater severity of pathology seen in women.

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Section: Sex and Autophagy Disruption In Alzheimer's Diseasementioning

confidence: 99%

Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease

Congdon

2018

Front. Neurosci.

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“…Moreover, direct or indirect interactions of α -syn and A β promote their mutual aggregation and accumulation, disturb the function of mitochondria, cause excessive glutamate release in the synapse, and eventually result in excitotoxicity and cell death in the brain [ 8 ]. That is, A β aggravates the neurotoxicity of α -syn in the brain [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Ceftriaxone Treatment for Neuronal Deficits: A Histological and MEMRI Study in a Rat Model of Dementia with Lewy Bodies

Weng

Lin

et al. 2018

Behavioural Neurology

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Dementia with Lewy bodies (DLB) is characterized by neuronal deficits and α-synuclein inclusions in the brain. Ceftriaxone (CEF), a β-lactam antibiotic, has been suggested as a therapeutic agent in several neurodegenerative disorders for its abilities to counteract glutamate-mediated toxicity and to block α-synuclein polymerization. By using manganese-enhanced magnetic resonance imaging (MEMRI) and immunohistochemistry, we measured the effects of CEF on neuronal activity and α-synuclein accumulation in the brain in a DLB rat model. The data showed that CEF corrected neuronal density and activity in the hippocampal CA1 area, suppressed hyperactivity in the subthalamic nucleus, and reduced α-synuclein accumulation, indicating that CEF is a potential agent in the treatment of DLB.

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“…It is widely accepted that neurodegenerative diseases are associated with chronic CNS inflammation . As an efficient inflammation amplifier, inflammasome activation could be the result of neurodegeneration as well as the reason for the disease progression.…”

Section: Inflammasome Activation In Microglia/macrophage Is the Resulmentioning

confidence: 99%

“…It is widely accepted that neurodegenerative diseases are associated with chronic CNS inflammation. 29,30 As an efficient inflam-…”

Section: Infl Amma Some Ac Tivati On In MI Crog Lia /Macrophag E Ismentioning

confidence: 99%

Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease

Lin

Zhang

et al. 2019

CNS Neurosci Ther

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Aging and aging‐related CNS diseases are associated with inflammatory status. As an efficient amplifier of immune responses, inflammasome is activated and played detrimental role in aging and aging‐related CNS diseases. Macrophage and microglia display robust inflammasome activation in infectious and sterile inflammation. This review discussed the impact of inflammasome activation in microglia/macrophage on senescence “inflammaging” and aging‐related CNS diseases. The preventive or therapeutic effects of targeting inflammasome on retarding aging process or tackling aging‐related diseases are also discussed.

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Aβ exacerbates α‐synuclein‐induced neurotoxicity through impaired insulin signaling in α‐synuclein‐overexpressed human SK‐N‐MC neuronal cells

Abstract: This raised the possibility that insulin resistance could be one of the causative factors of αSyn toxicity, and the strategies for insulin sensitization may have therapeutic potential for synucleinopathies including DLB.

Cited by 8 publications

References 39 publications

Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease

Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease

Ceftriaxone Treatment for Neuronal Deficits: A Histological and MEMRI Study in a Rat Model of Dementia with Lewy Bodies

Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease

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