Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-β deposition in a mouse model of Alzheimer’s disease

Lackie, Rachel E.; Marques-Lopes, José; Ostapchenko, Valeriy G.; Good, Sarah; Choy, Wing‐Yiu; Oosten-Hawle, Patricija van; Pasternak, Stephen; Prado, Marco A. M.

doi:10.1186/s40478-020-01013-5

Cited by 19 publications

(26 citation statements)

References 116 publications

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“…That said, some findings may contradict such a conclusion. Overexpression of STI1 in mice increased BACE 1 activity, decreased matrix metallopeptidase 2 (an Aβ-regulating enzyme) activity, increased amyloid burden and induced memory deficits in the 5XFAD AD mouse model (Lackie et al, 2020a). However, concerns aside over the relevance of such an extreme AD model, STI1 is not postulated here to directly control Aβ turnover but rather modulate oAβ42 interactions with PRPC.…”

Section: Molecular Control Of Oaβ42-dependent Modulation Of Memorymentioning

confidence: 92%

Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networks

Murphy¹

2021

Preprint

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Alzheimer’s Disease is defined as progressive memory loss coincident with accumulation of aggregated amyloid beta and phosphorylated tau. Identifying the relationship between these features has guided Alzheimer’s Disease research for decades, principally with the view that aggregated proteins drive a neurodegenerative process. Here I propose that amyloid beta and phospho-tau write-protect and tag neuroplastic changes as they form, protecting and insuring established neuroplasticity from corruption. In way of illustration, binding of oligomeric amyloid beta to the prion receptor is presented as an example possible mechanism. The write-protecting process is conjected to occur at least partially under the governance of isodendritic neuromodulators such as norepinephrine and acetylcholine. Coincident with aging, animals are exposed to accumulating amounts of memorable information. Compounded with recent increases in life expectancy and exposure to information-rich environments this causes aggregating proteins to reach unforeseen toxic levels as mnemonic circuits overload. As the brain cannot purposefully delete memories nor protect against overaccumulation of aggregating proteins, the result is catastrophic breakdown on cellular and network levels causing memory loss.

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Section: Molecular Control Of Oaβ42-dependent Modulation Of Memorymentioning

confidence: 92%

Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networks

Murphy¹

2021

Preprint

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“…A recent study challenged the neuroprotective role of STI1 in AD mouse models. Lackie et al showed that overexpression of STI1 in the 5xFAD mouse model exacerbated the AbO burden and increased memory deficits [211].…”

Section: Neurodegeneration 411 Alzheimer's Diseasementioning

confidence: 99%

With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage

Altınok

Sanchez‐Hodge

Stewart

et al. 2021

Cells

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Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintain protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensure cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, with a concentration on cardioprotection, neuroprotection, cancer, and autoimmune diseases. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones.

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Section: Alzheimer's Diseasementioning

confidence: 99%

With or Without You: Co-chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage

Altınok¹,

Sanchez‐Hodge²,

Stewart³

et al. 2021

Preprint

View full text Add to dashboard Cite

Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintaining protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensuring cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, focusing on cardioprotection, neuroprotection, and cancer. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones.

show abstract

Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-β deposition in a mouse model of Alzheimer’s disease

Cited by 19 publications

References 116 publications

Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networks

Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networks

With or without You: Co-Chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage

With or Without You: Co-chaperones Mediate Health and Disease by Modifying Chaperone Function and Protein Triage

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