Role of GTPases in the Regulation of Mitochondrial Dynamics in Alzheimer’s Disease and CNS-Related Disorders

Alexiou, Athanasios; Soursou, Georgia; Chatzichronis, Stylianos; Gasparatos, Ermis; Kamal, Mohammad Amjad; Yarla, Nagendra Sastry; Perveen, Asma; Barreto, George E.; Ashraf, Ghulam Md

doi:10.1007/s12035-018-1397-x

Cited by 27 publications

(12 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this review, we have illustrated the fundamental role of Mfn2 in mitochondrial function in health and disease, in particular in AD. Recently, different authors have indicated how perturbations in mitochondrial dynamics, particularly in fission and fusion proteins, Drp1, Fis1, OPA1, and Mfn2, can contribute to neuropathology [54][55][56].…”

Section: Mfn2 As a Potential Target In Alzheimer's Diseasementioning

confidence: 99%

Back to The Fusion: Mitofusin-2 in Alzheimer’s Disease

Sita

Hrelia

Graziosi

et al. 2020

JCM

View full text Add to dashboard Cite

Mitochondria are dynamic organelles that undergo constant fission and fusion. Mitochondria dysfunction underlies several human disorders, including Alzheimer's disease (AD). Preservation of mitochondrial dynamics is fundamental for regulating the organelle's functions. Several proteins participate in the regulation of mitochondrial morphology and networks, and among these, Mitofusin 2 (Mfn2) has been extensively studied. This review focuses on the role of Mfn2 in mitochondrial dynamics and in the crosstalk between mitochondria and the endoplasmic reticulum, in particular in AD. Understanding how this protein may be related to AD pathogenesis will provide essential information for the development of therapies for diseases linked to disturbed mitochondrial dynamics, as in AD.

show abstract

Section: Mfn2 As a Potential Target In Alzheimer's Diseasementioning

confidence: 99%

Back to The Fusion: Mitofusin-2 in Alzheimer’s Disease

Sita

Hrelia

Graziosi

et al. 2020

JCM

View full text Add to dashboard Cite

show abstract

“…The dynamin-like GTPases mitofusin 1 and mitofusin 2 (MFN1 and MFN2, respectively) initiate mitochondrial fusion by catalyzing the tethering and merging of outer membranes. Depletion of MFN1/2 leads to mitochondrial fragmentation and ultimately to mitochondrial dysfunction (19)(20)(21). In this study, we show that impairment of mitochondrial dynamics is closely associated with the exhaustion of both hypoxia-treated T cells and patient-derived TILs and that the exhaustion phenotype is induced through the miR-24-MYC-MFN1 axis.…”

Section: Introductionmentioning

confidence: 58%

Hypoxia Induces Mitochondrial Defect That Promotes T Cell Exhaustion in Tumor Microenvironment Through MYC-Regulated Pathways

et al. 2020

View full text Add to dashboard Cite

This protocol is described in detail in Supplemental Experimental Procedures. RNA Sequencing (RNA-Seq) and Analysis This protocol is described in detail in Supplemental Experimental Procedures. The RNA-seq data have been deposited in the NCBI Gene Expression Omnibus (GEO) under the Accession Code GSE110523. Real-Time RT-qPCR and Immunoblotting This protocol is described in detail in Supplemental Experimental Procedures.

show abstract

“…28,29 Dysfunction of mitochondrial fission or fusion can lead to severe neurodegeneration. [30][31][32] Increasing evidence shows that uncontrolled mitochondrial fission is an early phenomenon in cell necrosis. 33,34 Dynaminrelated protein 1 (Drp1), a strong GTPase, plays an important role in mitochondrial fission.…”

Section: Introductionmentioning

confidence: 99%

“…Mitochondrial dynamics are important for maintaining cell function, and their dysfunction leads to neuronal synapse loss 26,27 and cell death 28,29 . Dysfunction of mitochondrial fission or fusion can lead to severe neurodegeneration 30‐32 . Increasing evidence shows that uncontrolled mitochondrial fission is an early phenomenon in cell necrosis 33,34 .…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine exposure induces neuronal programmed necrosis by activating the receptor‐interacting protein kinase 3 ‐related signalling pathway

Zhao

Chen

et al. 2021

FASEB j.

View full text Add to dashboard Cite

Methamphetamine (METH) is a synthetic drug with severe neurotoxicity, however, the regulation of METH-induced neuronal programmed necrosis remains poorly understood. The aim of this study was to identify the molecular mechanisms of METHinduced neuronal programmed necrosis. We found that neuronal programmed necrosis occurred in the striatum of brain samples from human and mice that were exposed to METH. The receptor-interacting protein kinase 3 (RIP3) was highly expressed in the neurons of human and mice exposed to METH, and RIP3-silenced or RIP1-inhibited protected neurons developed neuronal programmed necrosis in vitro and in vivo following METH exposure. Moreover, the RIP1-RIP3 complex causes cell programmed necrosis by regulating mixed lineage kinase domain-like protein (MLKL)-mediated cell membrane rupture and dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Together, these data indicate that RIP3 plays an indispensable role in the mechanism of METH-induced neuronal programmed necrosis, which may represent a potential therapeutic target for METH-induced neurotoxicity. K E Y W O R D Sdynamin-related protein 1, methamphetamine, mixed lineage kinase domain-like protein, programmed necrosis, the receptor-interacting protein kinase 3The shRNA synthesis and stereotaxic injection protocol was based on our recent previous studies. 8,9,45 A short

show abstract

Role of GTPases in the Regulation of Mitochondrial Dynamics in Alzheimer’s Disease and CNS-Related Disorders

Cited by 27 publications

References 111 publications

Back to The Fusion: Mitofusin-2 in Alzheimer’s Disease

Back to The Fusion: Mitofusin-2 in Alzheimer’s Disease

Hypoxia Induces Mitochondrial Defect That Promotes T Cell Exhaustion in Tumor Microenvironment Through MYC-Regulated Pathways

Methamphetamine exposure induces neuronal programmed necrosis by activating the receptor‐interacting protein kinase 3 ‐related signalling pathway

Contact Info

Product

Resources

About