Parkin overexpression ameliorates hippocampal long-term potentiation and  -amyloid load in an Alzheimer's disease mouse model

Hong, Xiaoqi; Liu, Jie; Zhu, Guoqi; Zhuang, Yinghan; Suo, Haiyun; Wang, Pan; Huang, Dongping; Xu, Jing; Huang, Yu-Fang; Yu, Mei; Bian, Minjuan; Sheng, Zhejin; Fei, Jian; Song, Houyan; Behnisch, Thomas; Huang, Fang

doi:10.1093/hmg/ddt501

Cited by 59 publications

(46 citation statements)

References 72 publications

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“…A clinical study by Yokota et al demonstrated that TRIM32/ 37 upregulation in the occipital lobe may result in a gain-offunction of the UPS; therefore, this protective mechanism enables certain brain regions to become less susceptible to AD pathogenesis [118]. Interestingly, it has been reported that the overexpression of Parkin, an E3 ligase that is associated with familial PD, ameliorates Tau and Aβ aggregates in an AD mouse model [360]. This finding implies that the activity of canonical E3 ligases for Tau or Aβ can be compensated by other E3 ligases.…”

Section: Discussionmentioning

confidence: 99%

The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer’s Disease

Sulistio

Heese

2015

Mol Neurobiol

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One of the shared hallmarks of neurodegenerative diseases is the accumulation of misfolded proteins. Therefore, it is suspected that normal proteostasis is crucial for neuronal survival in the brain and that the malfunction of this mechanism may be the underlying cause of neurodegenerative diseases. The accumulation of amyloid plaques (APs) composed of amyloid-beta peptide (Aβ) aggregates and neurofibrillary tangles (NFTs) composed of misfolded Tau proteins are the defining pathological markers of Alzheimer's disease (AD). The accumulation of these proteins indicates a faulty protein quality control in the AD brain. An impaired ubiquitin-proteasome system (UPS) could lead to negative consequences for protein regulation, including loss of function. Another pivotal mechanism for the prevention of misfolded protein accumulation is the utilization of molecular chaperones. Molecular chaperones, such as heat shock proteins (HSPs) and FK506-binding proteins (FKBPs), are highly involved in protein regulation to ensure proper folding and normal function. In this review, we elaborate on the molecular basis of AD pathophysiology using recent data, with a particular focus on the role of the UPS and molecular chaperones as the defensive mechanism against misfolded proteins that have prion-like properties. In addition, we propose a rational therapy approach based on this mechanism.

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Section: Discussionmentioning

confidence: 99%

The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer’s Disease

Sulistio

Heese

2015

Mol Neurobiol

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“…Moreover, parkin expression results in Aβ reduction which can be dampened by proteasome inhibitors (Rosen et al, 2010). In addition, overexpression of parkin in APP/PS1 mouse models restores impaired long-term potentiation (LTP) and rescues behavioral abnormalities by reducing Aβ load and neuroinflammation (Hong et al, 2014). …”

Section: Dysregulation Of Ubiquitination In Neurodegenerative Diseasesmentioning

confidence: 99%

Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases

Zheng

Huang

Zhang

et al. 2016

Front. Aging Neurosci.

240

171

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The ubiquitin-proteasome system (UPS) is one of the major protein degradation pathways, where abnormal UPS function has been observed in cancer and neurological diseases. Many neurodegenerative diseases share a common pathological feature, namely intracellular ubiquitin-positive inclusions formed by aggregate-prone neurotoxic proteins. This suggests that dysfunction of the UPS in neurodegenerative diseases contributes to the accumulation of neurotoxic proteins and to instigate neurodegeneration. Here, we review recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease.

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“…Fbxo2, described above, has also been implicated in the turnover of the Beta-secretase protein BACE1 (Gong et al, 2010). Similarly, overexpression of the E3 ligase Parkin, described below for its role in PD, has been shown to reduce APP expression, Amyloid-Beta burden, and inflammation while also restoring the formation of long-term hippocampal synaptic potentiation in an AD mouse model (Hong et al, 2014). …”

Section: Ubiquitination In Neuropathologymentioning

confidence: 99%

Ubiquitin pathways in neurodegenerative disease

Atkin

Paulson

2014

Front. Mol. Neurosci.

124

106

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Control of proper protein synthesis, function, and turnover is essential for the health of all cells. In neurons these demands take on the additional importance of supporting and regulating the highly dynamic connections between neurons that are necessary for cognitive function, learning, and memory. Regulating multiple unique synaptic protein environments within a single neuron while maintaining cell health requires the highly regulated processes of ubiquitination and degradation of ubiquitinated proteins through the proteasome. In this review, we examine the effects of dysregulated ubiquitination and protein clearance on the handling of disease-associated proteins and neuronal health in the most common neurodegenerative diseases.

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Parkin overexpression ameliorates hippocampal long-term potentiation and -amyloid load in an Alzheimer's disease mouse model

Cited by 59 publications

References 72 publications

The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer’s Disease

The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer’s Disease

Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases

Ubiquitin pathways in neurodegenerative disease

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