Autophagic activity in neuronal cell death

Button, Robert W.; Luo, Shouqing; Rubinsztein, David C.

doi:10.1007/s12264-015-1528-y

Cited by 72 publications

(63 citation statements)

References 127 publications

(216 reference statements)

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“…Apoptosis involves the organized dismantling of cells to minimize damage to neighboring cells, while necrosis leads to release of intracellular debris which can stimulate inflammatory responses and damage surrounding cells through various mechanisms, for example, by generating excess ROS (54,55). We now understand there is considerable overlap between these pathways, and that necrotic cell death can be regulated (termed necroptosis, programmed necrosis, or caspase-independent programmed cell death) (11,(54)(55)(56)(57)(58)(59)(60). Autophagy, a lysosomal processes of cellular component recycling, is intimately associated with both cell death and survival mechanisms in ischemia (58,59,(61)(62)(63)(64)(65)(66).…”

Section: Cell Death After Cerebral Ischemiamentioning

confidence: 99%

“…We now understand there is considerable overlap between these pathways, and that necrotic cell death can be regulated (termed necroptosis, programmed necrosis, or caspase-independent programmed cell death) (11,(54)(55)(56)(57)(58)(59)(60). Autophagy, a lysosomal processes of cellular component recycling, is intimately associated with both cell death and survival mechanisms in ischemia (58,59,(61)(62)(63)(64)(65)(66). In fact, apoptosis, autophagy, programmed necrosis, and necrosis all occur in stroke, and some cells even exhibit multiple mechanisms simultaneously (10,60,67).…”

Section: Cell Death After Cerebral Ischemiamentioning

confidence: 99%

See 1 more Smart Citation

Ischemic Stroke Mechanisms, Prevention, and Treatment: The Anesthesiologist’s Perspective

McCrary¹,

Wang²,

Wei³

2017

J Anesth Perioper Med

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Section: Cell Death After Cerebral Ischemiamentioning

confidence: 99%

Section: Cell Death After Cerebral Ischemiamentioning

confidence: 99%

Ischemic Stroke Mechanisms, Prevention, and Treatment: The Anesthesiologist’s Perspective

McCrary¹,

Wang²,

Wei³

2017

J Anesth Perioper Med

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“…In this special issue, "Autophagy in Neural Function [15,[17][18][19][20][21][22][23][24][25][26][27][28] .…”

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confidence: 99%

“…However, in some contexts, dysregulation of autophagy may cause neurodegeneration and cell death [20,21] .…”

mentioning

confidence: 99%

“…Rubinsztein and colleagues [20] have provided an excellent review of this important field by analyzing several key fi ndings on autophagic cell death and they proposed a new model on how the extent of autophagy dictates the fate of neurons under stress, which quite nicely explains why autophagy can play opposing roles in neurons depending on the context. In addition to selective macroautophagy, chaperone-mediate autophagy (CMA), another type of selective autophagy, also plays an important role in neuronal survival, as many aggregate-prone proteins such as α-synuclein and tau serve as its targets.…”

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confidence: 99%

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Selective role of autophagy in neuronal function and neurodegenerative diseases

Rui

2015

Neurosci. Bull.

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·Editorial·Proteostasis is critical for neuronal maintenance and survival, and its imbalance leads to neurodegeneration with the hallmark of protein misfolding and aggregation [1] .Macroautophagy becomes a major route for the clearance of protein aggregates that are normally poor substrates for the proteasome, the other protein quality-control machinery [2] . As a fl ux process, macroautophagy (hereafter referred to as autophagy) involves the formation of the autophagosome, a double-membrane vesicle for engulfi ng unwanted cellular components such as protein aggregates, and the fusion of autophagosomes with lysosomes that contain many potent proteases for fi nal degradation [3] .In the past decades, the mechanism of autophagy has been intensively studied under starvation conditions. Autophagy is a hierarchical process involving the activation of ULK1, the initiating kinase, and many downstream events such as Beclin 1 complex activation and LC3 lipidation [3] . It has been well established that, during amino-acid starvation, mTOR, the master nutrient sensor, dissociates from and in turn activates ULK1 kinase [4] .Interestingly, upon energy starvation such as glucose depletion, the main energy sensor AMPK activates ULK1 through antagonizing mTOR-mediated ULK1 inhibitory phosphorylation [5] . It is generally believed that starvation induces non-selective autophagy that targets non-essential cellular components for degradation to provide building blocks for cellular survival in unfavorable conditions.In comparison with the well-characterized starvationinduced nonselective autophagy, the molecular mechanism of selective autophagy is largely unknown [6] . Selective autophagy is a comprehensive term that can be classifi ed into many different types such as aggrephagy, mitophagy, and lipophagy [7] . In particular, aggrephagy plays an important role in neuronal survival, as neurons are nondividing cells and cannot overcome cellular toxicity induced by protein aggregates through dilution effects. Therefore, aggrephagy becomes essential for neurons to preserve proteostasis. However, the underlying mechanism is yet to be uncovered. Recently, Huntingtin, the Huntington's disease gene product, was identifi ed as a scaffold protein for selective autophagy including aggrephagy, mitophagy, and lipophagy in mammalian cells, paving the way for further investigation in this emerging young field [8] . In addition, cargo receptor proteins such as p62 and NBR1 bring cargos to autophagosomes by interacting with the autophagosomal protein LC3 [9] . As both p62 and NBR1 contain ubiquitin-binding domains, the cargos modifi ed by lineage-specific ubiquitin play an important role in cargo recognition in selective autophagy. For instance, ubiquitin K63-modified substrates preferentially bind to p62 for autophagic degradation [10] .Selective autophagy has been linked to a variety of human diseases including but not limited to neurodegeneration and cancer [11] . For example, tau protein, implicated in Alzheimer's disease (AD), was shown to be ...

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Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

Uddin

Mamun

Labu

et al. 2018

Journal Cellular Physiology

121

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Autophagy is a preserved cytoplasmic self‐degradation process and endorses recycling of intracellular constituents into bioenergetics for the controlling of cellular homeostasis. Functional autophagy process is essential in eliminating cytoplasmic waste components and helps in the recycling of some of its constituents. Studies have revealed that neurodegenerative disorders may be caused by mutations in autophagy‐related genes and alterations of autophagic flux. Alzheimer’s disease (AD) is an irrevocable deleterious neurodegenerative disorder characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in the hippocampus and cortex. In the central nervous system of healthy people, there is no accretion of amyloid β (Aβ) peptides due to the balance between generation and degradation of Aβ. However, for AD patients, the generation of Aβ peptides is higher than lysis that causes accretion of Aβ. Likewise, the maturation of autophagolysosomes and inhibition of their retrograde transport creates favorable conditions for Aβ accumulation. Furthermore, increasing mammalian target of rapamycin (mTOR) signaling raises tau levels as well as phosphorylation. Alteration of mTOR activity occurs in the early stage of AD. In addition, copious evidence links autophagic/lysosomal dysfunction in AD. Compromised mitophagy is also accountable for dysfunctional mitochondria that raises Alzheimer’s pathology. Therefore, autophagic dysfunction might lead to the deposit of atypical proteins in the AD brain and manipulation of autophagy could be considered as an emerging therapeutic target. This review highlights the critical linkage of autophagy in the pathogenesis of AD, and avows a new insight to search for therapeutic target for blocking Alzheimer’s pathogenesis.

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Autophagic activity in neuronal cell death

Cited by 72 publications

References 127 publications

Ischemic Stroke Mechanisms, Prevention, and Treatment: The Anesthesiologist’s Perspective

Ischemic Stroke Mechanisms, Prevention, and Treatment: The Anesthesiologist’s Perspective

Selective role of autophagy in neuronal function and neurodegenerative diseases

Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

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