Autophagy in Parkinson's Disease

Hou, Xu; Watzlawik, Jens O.; Fiesel, Fabienne C.; Springer, Wolfdieter

doi:10.1016/j.jmb.2020.01.037

Cited by 260 publications

(167 citation statements)

References 245 publications

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“…Both PD-linked PINK1 and Parkin mutations prevent or impair the activation of mitophagy due to impaired PINK1 stabilization on the OMM, reduced PINK1 kinase activity, and/or compromised binding of PINK1 to Parkin. Studies in both mammalian cells and Drosophila confirm that mutations in the kinase domain of PINK1 fail to induce Parkin translocation to mitochondria (reviewed in Hou et al 2020). While the extent of PINK1/Parkin-mediated mitophagy in vivo seems to be quite low at basal levels (McWilliams et al 2018), its importance increases with age (Cornelissen et al 2018).…”

Section: The Pink1/parkin Pathway Of Mitophagymentioning

confidence: 96%

Kill one or kill the many: interplay between mitophagy and apoptosis

Wanderoy

Hees

Klesse

et al. 2020

Biological Chemistry

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Mitochondria are key players of cellular metabolism, Ca2+ homeostasis, and apoptosis. The functionality of mitochondria is tightly regulated, and dysfunctional mitochondria are removed via mitophagy, a specialized form of autophagy that is compromised in hereditary forms of Parkinson’s disease. Through mitophagy, cells are able to cope with mitochondrial stress until the damage becomes too great, which leads to the activation of pro-apoptotic BCL-2 family proteins located on the outer mitochondrial membrane. Active pro-apoptotic BCL-2 proteins facilitate the release of cytochrome c from the mitochondrial intermembrane space (IMS) into the cytosol, committing the cell to apoptosis by activating a cascade of cysteinyl-aspartate specific proteases (caspases). We are only beginning to understand how the choice between mitophagy and the activation of caspases is determined on the mitochondrial surface. Intriguingly in neurons, caspase activation also plays a non-apoptotic role in synaptic plasticity. Here we review the current knowledge on the interplay between mitophagy and caspase activation with a special focus on the central nervous system.

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Section: The Pink1/parkin Pathway Of Mitophagymentioning

confidence: 96%

Kill one or kill the many: interplay between mitophagy and apoptosis

Wanderoy

Hees

Klesse

et al. 2020

Biological Chemistry

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“…Schisandrin increases levels of TH expression and reduces inflammatory cytokines, however reduction of IL-1Beta and TNF-α were not found to be significant in this case. As in PD, MPTP can induce significant decreases in LC3-II , beclin1 , parkin , and PINK1 , all of which significantly resist depletion after treatment with schisandrin A, suggesting it enhances autophagy [ 124 , 125 , 126 ]. As another lignan, 7-hydroxymatairesinol, found in strawberries and sesame seeds, was recently shown to prevent striatal terminal loss and neuroinflammation in the substantia nigra, and decrease levels of microglial and astrocyte markers.…”

Section: Mechanisms Of Neuroprotectionmentioning

confidence: 99%

The Pathology of Parkinson’s Disease and Potential Benefit of Dietary Polyphenols

et al. 2020

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by a loss of dopaminergic neurons, leading to bradykinesia, rigidity, tremor at rest, and postural instability, as well as non-motor symptoms such as olfactory impairment, pain, autonomic dysfunction, impaired sleep, fatigue, and behavioral changes. The pathogenesis of PD is believed to involve oxidative stress, disruption to mitochondria, alterations to the protein α-synuclein, and neuroinflammatory processes. There is currently no cure for the disease. Polyphenols are secondary metabolites of plants, which have shown benefit in several experimental models of PD. Intake of polyphenols through diet is also associated with lower PD risk in humans. In this review, we provide an overview of the pathology of PD and the data supporting the potential neuroprotective capacity of increased polyphenols in the diet. Evidence suggests that the intake of dietary polyphenols may inhibit neurodegeneration and the progression of PD. Polyphenols appear to have a positive effect on the gut microbiome, which may decrease inflammation that contributes to the disease. Therefore, a diet rich in polyphenols may decrease the symptoms and increase quality of life in PD patients.

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“…Mutations in α-synuclein, such as the mutant SNCA A53T, result in significantly decreased lipidation of LC3 and increased activity of mTOR signaling pathway, which inhibit the autophagic flux and reduce removal of abnormal proteins (Jiang et al, 2013). Besides mutations in SNCA, other genetic forms of PD involve mutations in LRRK2, VPS35, PRKN, PINK1, and PARK7 (Hou et al, 2020). Different PD genes/mutations affect autophagic function and contribution of autophagic impairment to PD pathogenesis (Hou et al, 2020).…”

Section: Parkinson's Disease (Pd)mentioning

confidence: 99%

“…Besides mutations in SNCA, other genetic forms of PD involve mutations in LRRK2, VPS35, PRKN, PINK1, and PARK7 (Hou et al, 2020). Different PD genes/mutations affect autophagic function and contribution of autophagic impairment to PD pathogenesis (Hou et al, 2020).…”

Section: Parkinson's Disease (Pd)mentioning

confidence: 99%

Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases

Deng

Liu

et al. 2020

Front. Cell Dev. Biol.

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Autophagy has dual effects in human diseases: appropriate autophagy may protect cells from stress, while excessive autophagy may cause cell death. Additionally, close interactions exist between autophagy and the Golgi. This review outlines recent advances regarding the role of the Golgi apparatus in autophagy. The signaling processes of autophagy are dependent on the normal function of the Golgi. Specifically, (i) autophagy-related protein 9 is mainly located in the Golgi and forms new autophagosomes in response to stressors; (ii) Golgi fragmentation is induced by Golgirelated proteins and accompanied with autophagy induction; and (iii) the endoplasmic reticulum-Golgi intermediate compartment and the reticular trans-Golgi network play essential roles in autophagosome formation to provide a template for lipidation of microtubule-associated protein 1A/1B-light chain 3 and induce further ubiquitination. Golgi-related proteins regulate formation of autophagosomes, and disrupted formation of autophagy can influence Golgi function. Notably, aberrant autophagy has been demonstrated to be implicated in neurological diseases. Thus, targeted therapies aimed at protecting the Golgi or regulating Golgi proteins might prevent or ameliorate autophagy-related neurological diseases. Further studies are needed to investigate the potential application of Golgi therapy in autophagy-based neurological diseases.

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Autophagy in Parkinson's Disease

Cited by 260 publications

References 245 publications

Kill one or kill the many: interplay between mitophagy and apoptosis

Kill one or kill the many: interplay between mitophagy and apoptosis

The Pathology of Parkinson’s Disease and Potential Benefit of Dietary Polyphenols

Golgi Apparatus: A Potential Therapeutic Target for Autophagy-Associated Neurological Diseases

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