Autophagy induction in the treatment of Alzheimer's disease

Schmukler, Eran; Pinkas‐Kramarski, Ronit

doi:10.1002/ddr.21605

Cited by 34 publications

(19 citation statements)

References 71 publications

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“…e metabolism of Aβ and Tau is strongly associated with autophagy, regulating autophagy is regard as one of the most promising therapeutic strategies [34][35][36][37]. Under normal circumstances, activation or a certain degree of enhancement of autophagy can significantly eliminate Aβ deposition, promote Tau clearance, and alleviate neurodegeneration [34,38,39]. Some researchers added Aβ 1-42 to SH-SY5Y cells and found that it can cause a certain cytotoxic effect on the cells.…”

Section: Discussionmentioning

confidence: 99%

Vitis vinifera L. Flavones Regulate Hippocampal Neurons via Autophagy in APP/PS1 Alzheimer Model Mice

Zhang

Maimaiti

Aili

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Alzheimer’s disease (AD) is a neurodegenerative disease and our current treatment approach can only delay its course rather than cure it completely. Flavones from Vitis vinifera L. have been reported to promote synaptic plasticity and indirectly affect the expression of cholinergic neurotransmitters in a rat model of Alzheimer’s disease. Objective. The aim of the study is to explore the effect of Vitis vinifera L. in APP/PS1 Alzheimer model mice. Methods. APP/PS1 AD mice were used as the research subjects, and the mice were divided into a model group, donepezil group, VTF low-dose group, VTF medium-dose group, and VTF high-dose group. C57BL/6 mice served as a control group. The autophagosomes were observed by a transmission electron microscope, and the expressions of LC3I, LC3IIand Beclin-1 were determined by Western blotting. The results of qRT-PCR are consistent with Western blotting. Results. VTF can exert a positive regulatory effect on AD mice by inhibiting autophagy. Conclusion. Our study supports that intragastrically administration of VTF is effective and operable in Alzheimer’s disease mice, and that inhibition of excessive autophagy may be one of the potential reasons why VTF exerts a therapeutic effect on AD.

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Section: Discussionmentioning

confidence: 99%

Vitis vinifera L. Flavones Regulate Hippocampal Neurons via Autophagy in APP/PS1 Alzheimer Model Mice

Zhang

Maimaiti

Aili

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…mTORC1 signaling downregulates the activity of the ULK1 complex, thus repressing autophagy induction. mTORC1 signaling is further regulated by nutrient-sensing kinases such as the AMPK and Akt pathways [55]. Additionally, PI3K acts as a major upstream modulator of mTOR and can further regulate autophagy via different stimuli such as growth factors or insulin [56].…”

Section: Elegans: a Model For Researchmentioning

confidence: 99%

Sirtuins and Autophagy in Age-Associated Neurodegenerative Diseases: Lessons from the C. elegans Model

Naseer

Mir

Takács‐Vellai

et al. 2021

IJMS

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Age-associated neurodegenerative diseases are known to have “impaired protein clearance” as one of the key features causing their onset and progression. Hence, homeostasis is the key to maintaining balance throughout the cellular system as an organism ages. Any imbalance in the protein clearance machinery is responsible for accumulation of unwanted proteins, leading to pathological consequences—manifesting in neurodegeneration and associated debilitating outcomes. Multiple processes are involved in regulating this phenomenon; however, failure to regulate the autophagic machinery is a critical process that hampers the protein clearing pathway, leading to neurodegeneration. Another important and widely known component that plays a role in modulating neurodegeneration is a class of proteins called sirtuins. These are class III histone deacetylases (HDACs) that are known to regulate various vital processes such as longevity, genomic stability, transcription and DNA repair. These enzymes are also known to modulate neurodegeneration in an autophagy-dependent manner. Considering its genetic relevance and ease of studying disease-related endpoints in neurodegeneration, the model system Caenorhabditis elegans has been successfully employed in deciphering various functional outcomes related to critical protein molecules, cell death pathways and their association with ageing. This review summarizes the vital role of sirtuins and autophagy in ageing and neurodegeneration, in particular highlighting the knowledge obtained using the C. elegans model system.

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“…Autophagy plays a widespread role in both physiological and multiple pathological conditions, including cancer and neuronal disorders [ 17 ], and is extensively involved in the pathogenesis of AD [ 18 ]. Autophagy, a self-digesting mechanism, is an intracellular cleansing process characterized by the engulfment of malformed proteins and damaged cellular organelles by membrane-bound vesicles known as autophagosomes [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease

Rahman

et al. 2020

Biomedicines

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Alzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated degradation of cytoplasmic constituents, which plays a critical role in maintaining cellular homeostasis. Importantly, recent studies reported that dysregulation of autophagy is associated in the pathogenesis of AD, and therefore, autophagy modulation has gained attention as a promising approach to treat AD pathogenesis. In AD, both the maturation of autolysosomes and its retrograde transports have been obstructed, which causes the accumulation of autophagic vacuoles and eventually leads to degenerating and dystrophic neurites function. However, the mechanism of autophagy modulation in APP processing and its pathogenesis have not yet been fully elucidated in AD. In the early stage of AD, APP processing and Aβ accumulation-mediated autophagy facilitate the removal of toxic protein aggregates via mTOR-dependent and -independent pathways. In addition, a number of autophagy-related genes (Atg) and APP are thought to influence the development of AD, providing a bidirectional link between autophagy and AD pathology. In this review, we summarized the current observations related to autophagy regulation and APP processing in AD, focusing on their modulation associated with the AD progression. Moreover, we emphasizes the application of small molecules and natural compounds to modulate autophagy for the removal and clearance of APP and Aβ deposits in the pathological condition of AD.

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Autophagy induction in the treatment of Alzheimer's disease

Cited by 34 publications

References 71 publications

Vitis vinifera L. Flavones Regulate Hippocampal Neurons via Autophagy in APP/PS1 Alzheimer Model Mice

Vitis vinifera L. Flavones Regulate Hippocampal Neurons via Autophagy in APP/PS1 Alzheimer Model Mice

Sirtuins and Autophagy in Age-Associated Neurodegenerative Diseases: Lessons from the C. elegans Model

Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease

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