Increased autophagy in transgenic mice with a G93A mutant SOD1 gene

Morimoto, Nobutoshi; Nagai, Makiko; Ohta, Yasuyuki; Miyazaki, Kazunori; Kurata, Tomoko; Morimoto, Masaharu; Murakami, Tetsuro; Takehisa, Yasushi; Ikeda, Yoshio; Kamiya, Tetsuro; Abe, Kōji

doi:10.1016/j.brainres.2007.06.045

Cited by 200 publications

(136 citation statements)

References 32 publications

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“…Indeed, we observed increased levels of LC3II across disease progression corresponding with previous literature (Morimoto et al 2007, Li et al 2008, Tian et al 2011). Similarly we found elevated ULK1 phosphorylation at PND 90, suggesting that AMPK may signal cytoprotective mechanisms such as the clearance of protein aggregates (Hetz et al 2009, Crippa et al 2010.…”

Section: Discussionsupporting

confidence: 90%

“Preconditioning” with latrepirdine, an adenosine 5′-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1G93A mice

Coughlan

Mitchem

Hogg

et al. 2015

Neurobiology of Aging

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Section: Discussionsupporting

confidence: 90%

“Preconditioning” with latrepirdine, an adenosine 5′-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1G93A mice

Coughlan

Mitchem

Hogg

et al. 2015

Neurobiology of Aging

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“…13 The increased expression of cathepsins as well as the autophagic marker LC3-II in SOD1 mutant mice indicated the possible involvement of autophagy-lysosome pathway in the degradation of mutant SOD1. 5,14 In addition, Kabuta et al provided direct evidence that autophagy can degrade mutant SOD1 and reduce toxicity in vitro. 6 Although autophagy activation may help degrade abnormal proteins it may disturb the cell homeostasis and lead to cell death when autophagy is over activated.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with the work of Morimoto et al, 14 we examined not only the protein level of LC3-II in the spinal cord but also the LC3 distribution in the MNs of spinal cord, which provided us more detailed information regarding the status of autophagy in individual neurons. In addition, we conducted morphological study by EM imaging which is a more reliable assessment to determine the level of AVs in the MNs of spinal cord.…”

Section: Discussionmentioning

confidence: 99%

Altered macroautophagy in the spinal cord of SOD1 mutant mice

Liang¹,

Zhang²,

Le³

2008

Autophagy

158

101

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“…Autophagy plays a vital neuroprotective role in central nervous system neurons, as it facilitates the removal of aggregated ubiquitinated protein inclusions and is essential for the prevention of neurodegeneration [110,111]. Dysfunctional autophagy has been linked to many chronic proteinopathies, including frontotemporal dementia (FTD), amyotrophic lateral sclerosis, Parkinson's disease (PD), Huntington's disease (HD), and AD [1,[112][113][114][115][116][117][118][119].…”

Section: Ad Pathogenesis and Link To Autophagymentioning

confidence: 99%

Promoting Autophagic Clearance: Viable Therapeutic Targets in Alzheimer's Disease

Friedman

Qureshi

2015

Neurotherapeutics

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Many neurodegenerative disorders are characterized by the aberrant accumulation of aggregate-prone proteins. Alzheimer's disease (AD) is associated with the buildup of β-amyloid peptides and tau, which aggregate into extracellular plaques and neurofibrillary tangles, respectively. Multiple studies have linked dysfunctional intracellular degradation mechanisms with AD pathogenesis. One such pathway is the autophagy-lysosomal system, which involves the delivery of large protein aggregates/inclusions and organelles to lysosomes through the formation, trafficking, and degradation of double-membrane structures known as autophagosomes. Converging data suggest that promoting autophagic degradation, either by inducing autophagosome formation or enhancing lysosomal digestion, provides viable therapeutic strategies. In this review, we discuss compounds that can augment autophagic clearance and may ameliorate disease-related pathology in cell and mouse models of AD. Canonical autophagy induction is associated with multiple signaling cascades; on the one hand, the best characterized is mammalian target of rapamycin (mTOR). Accordingly, multiple mTOR-dependent and mTORindependent drugs that stimulate autophagy have been tested in preclinical models. On the other hand, there is a growing list of drugs that can enhance the later stages of autophagic flux by stabilizing microtubule-mediated trafficking, promoting lysosomal fusion, or bolstering lysosomal enzyme function. Although altering the different stages of autophagy provides many potential targets for AD therapeutic interventions, it is important to consider how autophagy drugs might also disturb the delicate balance between autophagosome formation and lysosomal degradation.

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Increased autophagy in transgenic mice with a G93A mutant SOD1 gene

Cited by 200 publications

References 32 publications

“Preconditioning” with latrepirdine, an adenosine 5′-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1G93A mice

“Preconditioning” with latrepirdine, an adenosine 5′-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1G93A mice

Altered macroautophagy in the spinal cord of SOD1 mutant mice

Promoting Autophagic Clearance: Viable Therapeutic Targets in Alzheimer's Disease

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