Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the Aβ42 transgenic Drosophila model

Lv, Fengshou; Yang, Xiaopeng; Cui, Chuanju; Su, Chunhe

doi:10.1371/journal.pone.0176183

Cited by 8 publications

(10 citation statements)

References 27 publications

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“…The second reason is that the decreased clearance of Aβ by some organelles and cellular functions such as the lysosome, proteasome, and autophagy. Hence, drugs which are capable for promoting the clearance or inhibiting the production of Aβ may be a promising therapeutic method toward AD (D. I. Kim et al, ; B. Kim, Park, Chang, & Lee, ; Lv, Yang, Cui, & Su, ; Pickett et al, ; Sarkar, Jun, & Simpkins, ; Yan et al, ).…”

Section: Drp1 and Neurodegenerative Diseasesmentioning

confidence: 99%

Dynamin‐related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases

Huang

Xie

et al. 2018

Journal Cellular Physiology

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Mitochondria play a key role in the maintenance of neuronal function by continuously providing energy. Here, we will give a detailed review about the recent developments in regards to dynamin‐related protein 1 (Drp1) induced unbalanced mitochondrial dynamics, excessive mitochondrial division, and neuronal injury in neural system dysfunctions and neurodegenerative diseases, including the Drp1 knockout induced mice embryonic death, the dysfunction of the Drp1‐dependent mitochondrial division induced neuronal cell apoptosis and impaired neuronal axonal transportation, the abnormal interaction between Drp1 and amyloid β (Aβ) in Alzheimer's disease (AD), the mutant Huntingtin (Htt) in Huntington's disease (HD), and the Drp1‐associated pathogenesis of other neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Drp1 is required for mitochondrial division determining the size, shape, distribution, and remodeling as well as maintaining of mitochondrial integrity in mammalian cells. In addition, increasing reports indicate that the Drp1 is involved in some cellular events of neuronal cells causing some neural system dysfunctions and neurodegenerative diseases, including impaired mitochondrial dynamics, apoptosis, and several posttranslational modification induced increased mitochondrial divisions. Recent studies also revealed that the Drp1 can interact with Aβ, phosphorylated τ, and mutant Htt affecting the mitochondrial shape, size, distribution, axonal transportation, and energy production in the AD and HD neuronal cells. These changes can affect the health of mitochondria and the function of synapses causing neuronal injury and eventually leading to the dysfunction of memory, cognitive impairment, resting tremor, posture instability, involuntary movements, and progressive muscle atrophy and paralysis in patients.

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Section: Drp1 and Neurodegenerative Diseasesmentioning

confidence: 99%

Dynamin‐related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases

Huang

Xie

et al. 2018

Journal Cellular Physiology

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“…The study holds significance as it was the first upstream effect of Drp1 on Aβ that was recognized. Surprisingly, Lv et al (2017) reported that exogenous expression of Drp1 in a transgenic Drosophila model of AD promote crawling ability and suppressed neurodegeneration. The results obtained by Lv et al (2017) contradict most of the studies as it suggests the protective role of Drp1 in AD.…”

Section: Role Of Drp1 In Admentioning

confidence: 99%

“…Surprisingly, Lv et al (2017) reported that exogenous expression of Drp1 in a transgenic Drosophila model of AD promote crawling ability and suppressed neurodegeneration. The results obtained by Lv et al (2017) contradict most of the studies as it suggests the protective role of Drp1 in AD. Altogether, these shreds of evidence recognized Drp1 as a key player in the pathogenesis of AD, and its inhibition could provide the possibility for a novel intervention for AD.…”

Section: Role Of Drp1 In Admentioning

confidence: 99%

Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease

Bera

Lavanya

Reshmi

et al. 2022

Eur J of Neuroscience

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Alzheimer's disease (AD), a progressive neurodegenerative disorder, has emerged as the most common form of dementia in the elderly. Two major pathological hallmarks have been identified for AD: extracellular amyloid plaques and intracellular neurofibrillary tangles (NFT). Recently, dynaminrelated protein 1 (Drp1) was recognized to contribute significantly towards the pathogenesis of AD. Drp1 is primarily located in the cytosol, from where it translocates to the mitochondrial outer membrane and drives the mitochondrial fission via GTP hydrolysis. Drp1 interacts with Aβ and phosphorylated tau, leading to excessive mitochondrial fragmentation, which in turn results in synaptic dysfunction, neuronal damage and cognitive decline. Several studies suggest an increase in the level of Drp1 in the post-mortem brain specimen collected from the AD patients and murine models of AD. Interestingly, heterozygous deletion of Drp1 in the transgenic murine model of AD ameliorates the mitochondrial dysfunction, improving learning and memory. The current review article discusses the possible mechanistic pathways by which Drp1 can influence the pathogenesis of AD. Besides, it will describe various inhibitors for Drp1 and their potential role as therapeutics for AD in the future.

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“…With the OK6 promoter, tau was specifically overexpressed in motoneurons to study its role in axonal functions [182]. With the Elav promoter, Aβ42 was overexpressed in all the neurons, decreasing the crawling ability and lifespan of flies [183]. Thus, Drosophila models show some of the AD hallmarks, i.e., Aβ aggregation, tau hyperphosphorylation, impaired synaptic activity [175], and neurodegeneration [176], but they cannot clearly recapitulate the disease, as seen in the previously described models.…”

Section: Drosophila Melanogastermentioning

confidence: 99%

Deconstructing Alzheimer’s Disease: How to Bridge the Gap between Experimental Models and the Human Pathology?

Vignon

Salvador-Prince

Lehmann

et al. 2021

IJMS

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Discovered more than a century ago, Alzheimer’s disease (AD) is not only still present in our societies but has also become the most common dementia, with 50 million people worldwide affected by the disease. This number is expected to double in the next generation, and no cure is currently available to slow down or stop the disease progression. Recently, some advances were made due to the approval of the aducanumab treatment by the American Food and Drug Administration. The etiology of this human-specific disease remains poorly understood, and the mechanisms of its development have not been completely clarified. Several hypotheses concerning the molecular mechanisms of AD have been proposed, but the existing studies focus primarily on the two main markers of the disease: the amyloid β peptides, whose aggregation in the brain generates amyloid plaques, and the abnormally phosphorylated tau proteins, which are responsible for neurofibrillary tangles. These protein aggregates induce neuroinflammation and neurodegeneration, which, in turn, lead to cognitive and behavioral deficits. The challenge is, therefore, to create models that best reproduce this pathology. This review aims at gathering the different existing AD models developed in vitro, in cellulo, and in vivo. Many models have already been set up, but it is necessary to identify the most relevant ones for our investigations. The purpose of the review is to help researchers to identify the most pertinent disease models, from the most often used to the most recently generated and from simple to complex, explaining their specificities and giving concrete examples.

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Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the Aβ42 transgenic Drosophila model

Cited by 8 publications

References 27 publications

Dynamin‐related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases

Dynamin‐related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases

Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease

Deconstructing Alzheimer’s Disease: How to Bridge the Gap between Experimental Models and the Human Pathology?

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