Stress response mechanisms in protein misfolding diseases: Profiling a cellular model of Huntington's disease

Almeida, Liliana M.; Oliveira, Â.; Oliveira, Jorge M. A.; Pinho, Brígida R.

doi:10.1016/j.abb.2023.109711

Cited by 5 publications

(3 citation statements)

References 95 publications

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“…The analysis of upstream regulators also reveals the altered expression of proteins that form intracellular aggregates under various stress conditions: HTT (Huntingtin), APP (amyloid Beta precursor), and MAPT (microtubule-associated protein tau) [61][62][63]. All of them are also involved in oxidative stress damage, highlighting the influence of temperature variation on thermal and oxidative stress responses in fish, consistent with previous descriptions [127,128].…”

Section: Analysis Of Upstream Regulatorssupporting

confidence: 85%

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The Neurotoxic Effect of Environmental Temperature Variation in Adult Zebrafish (Danio rerio)

Maffioli,

Nonnis,

Grassi Scalvini

et al. 2023

IJMS

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Neurotoxicity consists of the altered functionality of the nervous system caused by exposure to chemical agents or altered chemical–physical parameters. The neurotoxic effect can be evaluated from the molecular to the behavioural level. The zebrafish Danio rerio is a model organism used in many research fields, including ecotoxicology and neurotoxicology. Recent studies by our research group have demonstrated that the exposure of adult zebrafish to low (18 °C) or high (34 °C) temperatures alters their brain proteome and fish behaviour compared to control (26 °C). These results showed that thermal variation alters the functionality of the nervous system, suggesting a temperature-induced neurotoxic effect. To demonstrate that temperature variation can be counted among the factors that generate neurotoxicity, eight different protein datasets, previously published by our research group, were subjected to new analyses using an integrated proteomic approach by means of the Ingenuity Pathway Analysis (IPA) software (Release December 2022). The datasets consist of brain proteome analyses of wild type adult zebrafish kept at three different temperatures (18 °C, 26 °C, and 34 °C) for 4 days (acute) or 21 days (chronic treatment), and of BDNF+/− and BDNF−/− zebrafish kept at 26 °C or 34 °C for 21 days. The results (a) demonstrate that thermal alterations generate an effect that can be defined as neurotoxic (p value ≤ 0.05, activation Z score ≤ −2 or ≥2), (b) identify 16 proteins that can be used as hallmarks of the neurotoxic processes common to all the treatments applied and (c) provide three protein panels (p value ≤ 0.05) related to 18 °C, 34 °C, and BDNF depletion that can be linked to anxiety-like or boldness behaviour upon these treatments.

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Section: Analysis Of Upstream Regulatorssupporting

confidence: 85%

Section: Upstream Regulators' Analysismentioning

confidence: 99%

The Neurotoxic Effect of Environmental Temperature Variation in Adult Zebrafish (Danio rerio)

Maffioli,

Nonnis,

Grassi Scalvini

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Moreover, Hernández et al observed that the ATF5 transcription factor, the master regulator of the mtUPR, was sequestered in mtHtt aggregates in HD mice, C. elegans, and patients, mainly in the cortex and striatum in the case of mice and patients [254]. Almeida et al also observed decreased levels of mtUPR markers in PC12 cells expressing mtHtt [255]. On the other hand, Naia et al demonstrated that SIRT3 expression levels and activity were elevated in several in vitro and in vivo models of HD [256].…”

Section: Huntington's Diseasementioning

confidence: 99%

Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases

Cilleros-Holgado,

Gómez-Fernández,

Piñero-Pérez

et al. 2023

Biomolecules

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Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich’s Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. These findings underscore mtUPR’s role as a promising therapeutic target in combating these devastating disorders.

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Dual roles of UPRer and UPRmt in neurodegenerative diseases

Xu,

Liu,

Wang

et al. 2023

J Mol Med

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Stress response mechanisms in protein misfolding diseases: Profiling a cellular model of Huntington's disease

Cited by 5 publications

References 95 publications

The Neurotoxic Effect of Environmental Temperature Variation in Adult Zebrafish (Danio rerio)

The Neurotoxic Effect of Environmental Temperature Variation in Adult Zebrafish (Danio rerio)

Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases

Dual roles of UPRer and UPRmt in neurodegenerative diseases

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