Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease

Sanchez-Mirasierra, Irene; Ghimire, Saurav; Hernández-Díaz, Sergio; Soukup, Sandra‐Fausia

doi:10.3389/fcell.2022.921314

Cited by 12 publications

(9 citation statements)

References 172 publications

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“…At the same time, the growing knowledge of PD, the ALP mechanisms, and the link between this disease and this important cellular mechanism has allowed for the generation of animal models, promising new research and knowledge. Presently, multiple potential treatments to restore the critical mechanism of autophagy in PD are being clinically tested [188] and will soon provide answers on their capacity to act as disease modifiers in a pathology for which there is no curative treatment yet. In addition, the future should see the development of drugs targeting the mTOR pathway or other autophagy modulators, like TFEB and Beclin-1.…”

Section: Discussionmentioning

confidence: 99%

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Pathogenic Aspects and Therapeutic Avenues of Autophagy in Parkinson’s Disease

Kinet

Dehay

2023

Cells

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The progressive aging of the population and the fact that Parkinson’s disease currently does not have any curative treatment turn out to be essential issues in the following years, where research has to play a critical role in developing therapy. Understanding this neurodegenerative disorder keeps advancing, proving the discovery of new pathogenesis-related genes through genome-wide association analysis. Furthermore, the understanding of its close link with the disruption of autophagy mechanisms in the last few years permits the elaboration of new animal models mimicking, through multiple pathways, different aspects of autophagic dysregulation, with the presence of pathological hallmarks, in brain regions affected by Parkinson’s disease. The synergic advances in these fields permit the elaboration of multiple therapeutic strategies for restoring autophagy activity. This review discusses the features of Parkinson’s disease, the autophagy mechanisms and their involvement in pathogenesis, and the current methods to correct this cellular pathway, from the development of animal models to the potentially curative treatments in the preclinical and clinical phase studies, which are the hope for patients who do not currently have any curative treatment.

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Section: Discussionmentioning

confidence: 99%

“…In recent years, multiple treatments to restore autophagy have entered clinical testing phases [188]. Ambroxol may be a promising one; firstly, used as a cough syrup, it can enhance GCase activity, permit better lysosomal function, and decrease reactive oxygen species (ROS) apparition [189].…”

Section: Drugs Currently In Clinical Trialsmentioning

confidence: 99%

Pathogenic Aspects and Therapeutic Avenues of Autophagy in Parkinson’s Disease

Kinet

Dehay

2023

Cells

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“…Several autophagy-enhancing agents were tested in pre-clinical PD models [132,133]. These include drugs that affect the mTOR signaling pathway such as rapamycin, metformin, resveratrol, PREP inhibitor (KYP-2047), and isorhynchophylline.…”

Section: Targeting Autophagy As Therapeutic Approach In Pdmentioning

confidence: 99%

Autophagy in Parkinson’s Disease

Nechushtai,

Frenkel,

Pinkas-Kramarski

2023

Biomolecules

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Parkinson’s disease (PD) is a devastating disease associated with accumulation of α-synuclein (α-Syn) within dopaminergic neurons, leading to neuronal death. PD is characterized by both motor and non-motor clinical symptoms. Several studies indicate that autophagy, an important intracellular degradation pathway, may be involved in different neurodegenerative diseases including PD. The autophagic process mediates the degradation of protein aggregates, damaged and unneeded proteins, and organelles, allowing their clearance, and thereby maintaining cell homeostasis. Impaired autophagy may cause the accumulation of abnormal proteins. Incomplete or impaired autophagy may explain the neurotoxic accumulation of protein aggregates in several neurodegenerative diseases including PD. Indeed, studies have suggested the contribution of impaired autophagy to α-Syn accumulation, the death of dopaminergic neurons, and neuroinflammation. In this review, we summarize the recent literature on the involvement of autophagy in PD pathogenesis.

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“…This structure, called the autophagosome, contains the autophagic cargo. Finally, in the degradation stage, the autophagosome fuses with the lysosomal membrane and the autophagic cargo is sequestered by lysosomal hydrolases (Refs 15 , 16 , 17 ). In macroautophagy and microautophagy (also called endosomal microautophagy in mammals), cargo transport to the lysosome is vesicle-mediated, whereas in CMA it occurs through specific receptors (Refs 18 , 19 ).…”

Section: Autophagy and Agingmentioning

confidence: 99%

Autophagic mechanisms in longevity intervention: role of natural active compounds

Akça

Ayan

Çetinkaya

et al. 2023

Expert Rev. Mol. Med.

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The term ‘autophagy’ literally translates to ‘self-eating’ and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they might be connected to both aging and the onset and progression of disease. Additionally, we go over the most recent preclinical data supporting the use of autophagy modulators as age-related illnesses including cancer, cardiovascular and neurodegenerative diseases, and metabolic dysfunction. It is crucial to discover important targets in the autophagy pathway in order to create innovative therapies that effectively target autophagy. Natural products have pharmacological properties that can be therapeutically advantageous for the treatment of several diseases and they also serve as valuable sources of inspiration for the development of possible new small-molecule drugs. Indeed, recent scientific studies have shown that several natural products including alkaloids, terpenoids, steroids, and phenolics, have the ability to alter a number of important autophagic signalling pathways and exert therapeutic effects, thus, a wide range of potential targets in various stages of autophagy have been discovered. In this review, we summarised the naturally occurring active compounds that may control the autophagic signalling pathways.

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Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease

Cited by 12 publications

References 172 publications

Pathogenic Aspects and Therapeutic Avenues of Autophagy in Parkinson’s Disease

Pathogenic Aspects and Therapeutic Avenues of Autophagy in Parkinson’s Disease

Autophagy in Parkinson’s Disease

Autophagic mechanisms in longevity intervention: role of natural active compounds

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