Shaping the Nrf2-ARE-related pathways in Alzheimer’s and Parkinson’s diseases

Fão, Lígia; Mota, Sandra I.; Rego, A. Cristina

doi:10.1016/j.arr.2019.100942

Cited by 191 publications

(115 citation statements)

References 257 publications

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“…Tanji et al revealed that the ratio of phosphorylated (Ser349) p62 to total p62 was considerably increased in the brains of AD patients compared to controls [ 104 ]. The role of Nrf2 in Alzheimer disease has been well described in a comprehensive review by Fão et al [ 105 ].…”

Section: Neurojanus Role Of P62mentioning

confidence: 99%

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

Emanuele

Lauricella

D’Anneo

et al. 2020

IJMS

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p62 is a versatile protein involved in the delicate balance between cell death and survival, which is fundamental for cell fate decision in the context of both cancer and neurodegenerative diseases. As an autophagy adaptor, p62 recognizes polyubiquitin chains and interacts with LC3, thereby targeting the selected cargo to the autophagosome with consequent autophagic degradation. Beside this function, p62 behaves as an interactive hub in multiple signalling including those mediated by Nrf2, NF-κB, caspase-8, and mTORC1. The protein is thus crucial for the control of oxidative stress, inflammation and cell survival, apoptosis, and metabolic reprogramming, respectively. As a multifunctional protein, p62 falls into the category of those factors that can exert opposite roles in the cells. Chronic p62 accumulation was found in many types of tumors as well as in stress granules present in different forms of neurodegenerative diseases. However, the protein seems to have a Janus behaviour since it may also serve protective functions against tumorigenesis or neurodegeneration. This review describes the diversified roles of p62 through its multiple domains and interactors and specifically focuses on its oncoJanus and neuroJanus roles.

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Section: Neurojanus Role Of P62mentioning

confidence: 99%

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

Emanuele

Lauricella

D’Anneo

et al. 2020

IJMS

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“…This gap in knowledge about functions of BACH1 in AD needs to be fulfilled in future studies, particularly in light of the role for HO1 and reduced antioxidant response in the onset and progression of AD pathology [60,61,75]. While HO-1 and NQO1 protein proteins levels are elevated in AD brain (reviewed in [61,76]), reduced Nrf2 activity was reported in a number of studies performed on human and animal samples. Indeed, reduced Nrf2 nuclear expression in hippocampal samples from AD subjects were observed [77].…”

Section: Involvement Of Bach1 In Ad and Dsmentioning

confidence: 99%

The BACH1/Nrf2 Axis in Brain in Down Syndrome and Transition to Alzheimer Disease-Like Neuropathology and Dementia

et al. 2020

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Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses. Published studies from our laboratories propose that increased oxidative damage occurs early in life in DS population and contributes to age-dependent neurodegeneration. This is the result of damaged, oxidized proteins that belong to degradative systems, antioxidant defense system, neuronal trafficking. and energy metabolism. This review focuses on a key element that regulates redox homeostasis, the transcription factor Nrf2, which is negatively regulated by BACH1, encoded on chromosome 21. The role of the Nrf2/BACH1 axis in DS is under investigation, and the effects of triplicated BACH1 on the transcriptional regulation of Nrf2 are still unknown. In this review, we discuss the physiological relevance of BACH1/Nrf2 signaling in the brain and how the dysfunction of this system affects the redox homeostasis in DS neurons and how this axis may contribute to the transition of DS into DS with AD neuropathology and dementia. Further, some of the evidence collected in AD regarding the potential contribution of BACH1 to neurodegeneration in DS are also discussed.

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“…Nrf2 expression is low in AD animal models and AD patient brains [185]. Nrf2 binding to the ARE occurs soon during disease progression, which corresponds with an increase in ROS production [186]. Nrf2 neuroprotects by decreasing ROS generation and Aβ-mediated ROS-induced toxicity [187,188].…”

Section: Mitochondrial Well-functionmentioning

confidence: 99%

Endogenous Mechanisms of Neuroprotection: To Boost or Not to Be

Marmolejo-Martínez-Artesero

Casas

2021

Cells

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Postmitotic cells, like neurons, must live through a lifetime. For this reason, organisms/cells have evolved with self-repair mechanisms that allow them to have a long life. The discovery workflow of neuroprotectors during the last years has focused on blocking the pathophysiological mechanisms that lead to neuronal loss in neurodegeneration. Unfortunately, only a few strategies from these studies were able to slow down or prevent neurodegeneration. There is compelling evidence demonstrating that endorsing the self-healing mechanisms that organisms/cells endogenously have, commonly referred to as cellular resilience, can arm neurons and promote their self-healing. Although enhancing these mechanisms has not yet received sufficient attention, these pathways open up new therapeutic avenues to prevent neuronal death and ameliorate neurodegeneration. Here, we highlight the main endogenous mechanisms of protection and describe their role in promoting neuron survival during neurodegeneration.

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Shaping the Nrf2-ARE-related pathways in Alzheimer’s and Parkinson’s diseases

Cited by 191 publications

References 257 publications

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

The BACH1/Nrf2 Axis in Brain in Down Syndrome and Transition to Alzheimer Disease-Like Neuropathology and Dementia

Endogenous Mechanisms of Neuroprotection: To Boost or Not to Be

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