The Latest Articles on Autophagy and Neurodegenerative Diseases
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Autophagy and Neurodegenerative Diseases.
Title: Activation of ROS-PERK-TFEB by Filbertone Ameliorates Neurodegenerative Diseases via Enhancing the Autophagy-Lysosomal Pathway
Authors: Jeongmin Park, Jeong Heon Gong, Yubing Chen, Thu-Hang Thi Nghiem, Sonam Chandrawanshi, Eunyeong Hwang, Chae Ha Yang, Byung-Sam Kim, Jeong Woo Park, Stefan W. Ryter, Byungyong Ahn, Yeonsoo Joe, Yeonsoo Joe, Rina Yu
Type: Research Article
Abstract:
The molecular mechanisms underlying the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD), and Huntington's disease remain enigmatic, resulting in an unmet need for therapeutics development. Here, we suggest that filbertone, a key flavor compound found in the fruits of hazel trees of the genus Corylus, can ameliorate PD via lowering the abundance of aggregated α-synuclein. We previously reported that inhibition of hypothalamic inflammation by filbertone is mediated by suppression of nuclear factor kappa-B (NF-κB). Here, we report that filbertone activates PERK through mitochondrial ROS (mtROS) production, resulting in the increased nuclear translocation of transcription factor-EB (TFEB) in SH-SY5Y human neuroblastoma cells. TFEB activation by filbertone promotes the autophagy-lysosomal pathway (ALP), which in turn alleviates the accumulation of α-synuclein. We also demonstrate that filbertone prevented the loss of dopaminergic neurons in the substantia nigra and striatum of mice on high-fat diet (HFD). Filbertone treatment also reduced HFD-induced α-synuclein accumulation through upregulation of the ALP pathway. In addition, filbertone improved behavioral abnormalities (i.e., latency time to fall and decrease of running distance) in the MPTP-induced PD murine model. In conclusion, filbertone may show promise as a potential therapeutic for neurodegenerative disease.
Access this article: https://doi.org/10.1016/j.jnutbio.2023.109325
Title: Lithium engages autophagy for neuroprotection and neuroplasticity: translational evidence for therapy
Authors: Stefano Puglisi-Allegra, Gloria Lazzeri, Gloria Lazzeri, Filippo S. Giorgi, Francesca Biagioni, Francesco Fornai
Type: Review
Abstract:
Here an overview is provided on therapeutic/neuroprotective effects of Lithium (Li+) in neurodegenerative and psychiatric disorders focusing on the conspicuous action of Li+ through autophagy. The effects on the autophagy machinery remain the key molecular mechanisms to explain the protective effects of Li+ for neurodegenerative diseases, offering potential therapeutic strategies for the treatment of neuropsychiatric disorders and emphasizes a crossroad linking autophagy, neurodegenerative disorders, and mood stabilization.
Sensitization by psychostimulants points to several mechanisms involved in psychopathology, most also crucial in neurodegenerative disorders. Evidence shows the involvement of autophagy and metabotropic Glutamate receptors-5 (mGluR5) in neurodegeneration due to methamphetamine neurotoxicity as well as in neuroprotection, both in vitro and in vivo models.
More recently, Li+ was shown to modulate autophagy through its action on mGluR5, thus pointing to an additional way of autophagy engagement by Li+ and to a substantial role of mGluR5 in neuroprotection related to neural e neuropsychiatry diseases.
We propose Li+ engagement of autophagy through the canonical mechanisms of autophagy machinery and through the intermediary of mGluR5.
Access this article: https://doi.org/10.1016/j.neubiorev.2023.105148
Title: Corynoxine B targets at HMGB1/2 to enhance autophagy for alpha-synuclein clearance in fly and rodent models of Parkinson’s disease
Authors: Qi Zhu, Juxian Song, Juxian Song, Zhenwei Yuan, Zhenwei Yuan, Liangfeng Liu, Liming Xie, Qiwen Liao, Richard D. Ye, Xiu Chen, Yepiao Yan, Jieqiong Tan, Chris Soon Heng Tan, Min Li, Jiahong Lu
Type: Research Article
Abstract:
arkinson’s disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.
Access this article: https://doi.org/10.1016/j.apsb.2023.03.011
Title: Cross-talk between traditional Chinese medicine and Parkinson's disease based on cell autophagy
Authors: Mufei Wang, Hongsong Yu, Yihuai He, Shusheng Liao, Delin Xu
Type: Review
Abstract:
Background
Parkinson's disease (PD) is the second most common neurodegenerative movement disorder, with an unclear specific pathogenesis. There is no existing method that can reverse the development of PD. Importantly, researchers need to explore a new treatment rapidly for PD.
Methods
The literature search was performed in the past 10 years in PubMed and China National Knowledge Infrastructure (CNKI) on the treatment of PD via autophagy regulation, expands the dialectical thinking of traditional Chinese medicines (TCMs) for PD, and systematically assesses the pharmacological mechanism of TCMs and their compound preparations in the therapy of this disease.
Results
Previous studies have reported that TCMs exert neuroprotective effects by regulating autophagy. TCMs can be multitargeted to impact autophagy, alleviating symptoms in patients with PD.
Conclusion
This study can provide novel ideas and a theoretical basis for the treatment of PD.
Access this article: https://doi.org/10.1016/j.prmcm.2023.100235
Title: Acupuncture inhibits autophagy and repairs synapses by activating the mTOR pathway in Parkinson’s disease depression model rats
Authors: Baile Ning, Zhifang Wang, Qian Wu, Qiyue Deng, Qing Yang, Jing Gao, Wen Fu, Ying Deng, Bingxin Wu, Xichang Huang, Jilin Mei, Wenbin Fu
Type: Research Article
Abstract:
Acupuncture is a good treatment for depression in Parkinson's disease (DPD), so the possible mechanism of acupuncture in the treatment of DPD was explored in this study. Firstly, observing the behavioral changes of the DPD rat model, the regulation of monoamine neurotransmitters dopamine (DA) and 5-hydroxytryptamine (5-HT) in the midbrain, the change of α-synuclein (α-syn) in the striatum, the efficacy of acupuncture in the treatment of DPD was discussed. Secondly, autophagy inhibitors and activators were selected to judge the effect of acupuncture on autophagy in the DPD rat model. Finally, an mTOR inhibitor was used to observe the effect of acupuncture on the mTOR pathway in the DPD rat model. The results showed that acupuncture could improve the motor and depressive symptoms of DPD model rats, increase the content of DA and 5-HT, and decrease the content of ɑ-syn in the striatum. Acupuncture inhibited the expression of autophagy in the striatum of DPD model rats. At the same time, acupuncture upregulates p-mTOR expression, inhibits autophagy, and promotes synaptic protein expression. Therefore, we concluded that acupuncture might improve the behavior of DPD model rats by activating the mTOR pathway, inhibiting autophagy from removing α-syn and repairing synapses.
Access this article: https://doi.org/10.1016/j.brainres.2023.148320
