Heat Shock Proteins and Protein Quality Control in Alzheimer’s Disease

Leeuwen, Fred W. van; Kampinga, Harm H.

doi:10.1016/b978-0-12-811304-2.00010-9

Cited by 5 publications

(5 citation statements)

References 199 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This degradation was inhibited by proteasome inhibitors (Figure f and Supplementary Figure 5c). Our results are consistent with previous observations that proteasomal degradation is involved in the clearance of unstable Aβ42 . When present in low concentrations, soluble Aβ42 has been found to be efficiently cleared by the quality control machinery, especially the ubiquitin proteasome system, whose reduced function has been implicated in Alzheimer’s disease .…”

Section: Resultssupporting

confidence: 93%

“…Increased steady state levels of Aβ42 are known to enhance primary nucleation events, a prerequisite for Aβ42-associated disease states . Understanding and enhancing the degradation of the Aβ peptide has been suggested as a strategy for targeting Alzheimer’s disease . As our phenotypic readout for WT Aβ42 tripartite fusions involves proteolytic processing of Aβ42, our method may be useful in further exploring the stability of intracellular Aβ42.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Yeast Tripartite Biosensors Sensitive to Protein Stability and Aggregation Propensity

et al. 2020

View full text Add to dashboard Cite

In contrast to the myriad approaches available to study protein misfolding and aggregation in vitro, relatively few tools are available for the study of these processes in the cellular context. This is in part due to the complexity of the cellular environment which, for instance, interferes with many spectroscopic approaches. Here, we describe a tripartite fusion approach that can be used to assess in vivo protein stability and solubility in the cytosol of Saccharomyces cerevisiae. Our biosensors contain tripartite fusions in which a protein of interest is inserted into antibiotic resistance markers. These fusions act to directly link the aggregation susceptibility and stability of the inserted protein to antibiotic resistance. We demonstrate a linear relationship between the thermodynamic stabilities of variants of the model folding protein immunity protein 7 (Im7) fused into the resistance markers and their antibiotic resistance readouts. We also use this system to investigate the in vivo properties of the yeast prion proteins Sup35 and Rnq1 and proteins whose aggregation is associated with some of the most prevalent neurodegenerative misfolding disorders, including peptide amyloid beta 1−42 (Aβ42), which is involved in Alzheimer's disease, and protein α-synuclein, which is linked to Parkinson's disease.

show abstract

Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Yeast Tripartite Biosensors Sensitive to Protein Stability and Aggregation Propensity

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Finally, NPY has been shown to increase the expression and release of heat shock proteins (HSPs) involved in the preservation of muscle function (Gehrig et al., 2012; Panossian, Wikman, Kaur, & Asea, 2012). HSPs are molecular chaperones that are essential for protein quality control, as they guide protein folding, but also assist with proper protein clearance (van Leeuwen & Kampinga, 2018). HSPs work in collaboration with protein degradation systems, such as autophagy and the UPS, to maintain protein homoeostasis (Dokladny, Myers, & Moseley, 2015; Thakur & Nehru, 2014).…”

Section: Npy’s Impact On Pathogenic Als Mechanismsmentioning

confidence: 99%

Pathogenic or protective? Neuropeptide Y in amyotrophic lateral sclerosis

Clark

Hoyle

et al. 2020

Journal of Neurochemistry

View full text Add to dashboard Cite

Neuropeptide Y (NPY) is an endogenous peptide of the central and enteric nervous systems which has gained significant interest as a potential neuroprotective agent for treatment of neurodegenerative disease. Amyotrophic lateral sclerosis (ALS) is an aggressive and fatal neurodegenerative disease characterized by motor deficits and motor neuron loss. In ALS, recent evidence from ALS patients and animal models has indicated that NPY may have a role in the disease pathogenesis. Increased NPY levels were found to correlate with disease progression in ALS patients. Similarly, NPY expression is increased in the motor cortex of ALS mice by end stages of the disease. Although the functional consequence of increased NPY levels in ALS is currently unknown, NPY has been shown to exert a diverse range of neuroprotective roles in other neurodegenerative diseases; through modulation of potassium channel activity, increased production of neurotrophins, inhibition of endoplasmic reticulum stress and autophagy, reduction of excitotoxicity, oxidative stress, neuroinflammation and hyperexcitability. Several of these mechanisms and signalling pathways are heavily implicated in the pathogenesis of ALS. Therefore, in this review, we discuss possible effects of NPY and NPY‐receptor signalling in the ALS disease context, as determining NPY’s contribution to, or impact on, ALS disease mechanisms will be essential for future studies investigating the NPY system as a therapeutic strategy in this devastating disease.

show abstract

“…Dysregulation of molecular chaperones is shown to result in reduced Tau degradation and formation of neurotoxic Tau aggregates. 82 , 83 Thus, the upregulation of these molecular chaperones by light stimulation could reflect a mechanism of mitigation of the accumulation of AD‐related pathological molecules through the enhancement of their degradation. Accordingly, autophagy was also shown to be triggered by PBM treatment in AD transgenic mice 43 that may help in the degradation of Aβ and Tau pathological aggregates, leading to the recovery of neuronal malfunction.…”

Section: Discussionmentioning

confidence: 99%

“…When this is not possible (as occurs in heavily misfolded/aggregated proteins such as pathological Tau), HSPs deliver protein aggregates to proteasome or autophagosome for degradation. Dysregulation of molecular chaperones is shown to result in reduced Tau degradation and formation of neurotoxic Tau aggregates 82,83 . Thus, the upregulation of these molecular chaperones by light stimulation could reflect a mechanism of mitigation of the accumulation of AD‐related pathological molecules through the enhancement of their degradation.…”

Section: Discussionmentioning

confidence: 99%

Photobiomodulation and visual stimulation against cognitive decline and Alzheimer's disease pathology: A systematic review

Monteiro

Carvalho

Sousa

et al. 2022

A&D Transl Res & Clin Interv

View full text Add to dashboard Cite

Introduction Given the ineffectiveness of the available drug treatment against Alzheimer disease (AD), light‐based therapeutic modalities have been increasingly receiving attention with photobiomodulation (PBM) and, more recently, visual stimulation (VS) being among the most promising approaches. However, the PBM and VS light parameters tested so far, as well as their outcomes, vary a lot with conflicting results being reported. Methods Based on Scopus, PubMed, and Web of Science databases search, this systematic review summarizes, compares, and discusses 43 cell, animal, and human studies of PBM and VS related to cognitive decline and AD pathology. Results Preclinical work suggests that PBM with 640±30‐nm light and VS at 40 Hz attenuates Aβ and Tau pathology and improves neuronal and synaptic plasticity with most studies pointing towards enhancement of degradation/clearance mechanisms in the brain of AD animal models. Despite the gap of the translational evidence for both modalities, the few human studies performed so far support the use of PBM at 810‐870 nm light pulsing at 40 Hz for improving brain network connectivity and memory in older subjects and AD patients, while 40 Hz VS in humans seems to improve cognition; further clinical investigation is urgently required to clarify the beneficial impact of PBM and VS in AD patients. Discussion This review highlights PBM and VS as promising light‐based therapeutic approaches against AD brain neuropathology and related cognitive decline, clarifying the most effective light parameters for further preclinical and clinical testing and use. Highlights Light‐based brain stimulation produces neural entrainment and reverts neuronal damage Brain PBM and VS attenuate AD neuropathology PMB and VS are suggested to improve cognitive performance in AD patients and animal models Light stimulation represents a promising therapeutic strategy against neurodegeneration

show abstract

Heat Shock Proteins and Protein Quality Control in Alzheimer’s Disease

Cited by 5 publications

References 199 publications

Yeast Tripartite Biosensors Sensitive to Protein Stability and Aggregation Propensity

Yeast Tripartite Biosensors Sensitive to Protein Stability and Aggregation Propensity

Pathogenic or protective? Neuropeptide Y in amyotrophic lateral sclerosis

Photobiomodulation and visual stimulation against cognitive decline and Alzheimer's disease pathology: A systematic review

Contact Info

Product

Resources

About