The Latest Articles on Mitochondria in 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 mitochondria in neurodegenerative diseases.
Title: Mitochondria-lysosome-extracellular vesicles axis and nanotheranostics in neurodegenerative diseases
Authors: Liang Kou, Yiming Wang, Jingwen Li, Wenkai Zou, Zongjie Jin, Sijia Yin, Xiaosa Chi, Yadi Sun, Jiawei Wu, Tao Wang, Yun Xia
Type: Research Article
Abstract:
The intricate functional interactions between mitochondria and lysosomes play a pivotal role in maintaining cellular homeostasis and proper cellular functions. This dynamic interplay involves the exchange of molecules and signaling, impacting cellular metabolism, mitophagy, organellar dynamics, and cellular responses to stress. Dysregulation of these processes has been implicated in various neurodegenerative diseases. Additionally, mitochondrial-lysosomal crosstalk regulates the exosome release in neurons and glial cells. Under stress conditions, neurons and glial cells exhibit mitochondrial dysfunction and a fragmented network, which further leads to lysosomal dysfunction, thereby inhibiting autophagic flux and enhancing exosome release. This comprehensive review synthesizes current knowledge on mitochondrial regulation of cell death, organelle dynamics, and vesicle trafficking, emphasizing their significant contributions to neurodegenerative diseases. Furthermore, we explore the emerging field of nanomedicine in the management of neurodegenerative diseases. The review provides readers with an insightful overview of nano strategies that are currently advancing the mitochondrial-lysosome-extracellular vesicle axis as a therapeutic approach for mitigating neurodegenerative diseases.
Access this article: https://doi.org/10.1016/j.expneurol.2024.114757
Title: Interplay of mitochondria associated membrane proteins and autophagy: Implications in neurodegeneration
Authors: Prakash G. Kulkarni, Vaibhavi M. Mohire, Pranjal P. Waghmare, Tanushree Banerjee
Type: Review Article
Abstract
Since the discovery of membrane contact sites between ER and mitochondria called mitochondria-associated membranes (MAMs), several pieces of evidence identified their role in the regulation of different cellular processes such as Ca2+ signalling, mitochondrial transport, and dynamics, ER stress, inflammation, glucose homeostasis, and autophagy. The integrity of these membranes was found to be essential for the maintenance of these cellular functions. Accumulating pieces of evidence suggest that MAMs serve as a platform for autophagosome formation. However, the alteration within MAMs’ structure is associated with the progression of neurodegenerative diseases. Dysregulated autophagy is a hallmark of neurodegeneration. Here, in this review, we highlight the present knowledge on MAMs, their structural composition, and their roles in different cellular functions. We also discuss the association of MAMs proteins with impaired autophagy and their involvement in the progression of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.
Access this article: https://doi.org/10.1016/j.mito.2024.101874
Title: New perspectives on the role of mitochondria in Parkinson’s disease
Authors: Shiyi Yin, Yongjiang Zhang, Jiannan Wu, Run Song, Mengmeng Shen, Xiaoyi Lai, Junqiang Yan
Type: Review Article
Abstract:
Mitochondrial dysfunction is pivotal in the occurrence and development of Parkinson’s disease (PD). Interventions to increase mitochondrial biogenesis and maintain the balance in mitochondrial turnover have the potential to protect against neurological damage. In addition to their crucial role in the tricarboxylic acid cycle, mitochondria impact diverse activities, including cellular metabolism, cellular quality control, and the production of reactive oxygen species. Thus, it has become imperative to better understand the regulation and function of mitochondria in PD. With this review, we aim to stimulate research that explores mitochondria-oriented neuroprotection strategies to maintain the balance in mitochondrial turnover. First, we summarize research on newly discovered genes that regulate PD mitochondrial autophagy through PTEN-induced kinase 1 (PINK1), namely AMBRA1, SYNJ2BP, and SIAH3. Second, we review PD-related mitochondrial proteins, including STRT3 and SIRT6, and the mitochondrial unfolded protein response, covering their mechanisms of involvement in PD. Third, we emphasize the roles of the mitochondrial complex, pyroptosis, and copper-induced cell death in mitochondrial damage in PD. Finally, we present a brief overview of new therapeutic strategies to correct mitochondrial defects that may be applicable for targeting mitochondria in PD patients.
Access this article: https://doi.org/10.1016/j.jnrt.2024.100112
Title: Involvement of mitochondria in Alzheimer’s disease pathogenesis and their potential as targets for phytotherapeutics
Authors: Swathi Maruthiyodan, Kamalesh Dattaram Mumbrekar, Kanive Parashiva Guruprasad
Type: Review Article
Abstract:
Alzheimer's disease (AD) is the leading cause of dementia around the globe. The disease's genesis is multifaceted, and its pathophysiology is complicated. Malfunction of mitochondria has been regarded as one of the intracellular events that are substantially damaged in the onset of AD and are likely a common trait of other neurodegenerative illnesses. Several mitochondrial characteristics begin to diminish with age, eventually reaching a state of significant functional failure concurrent with the beginning of neurodegenerative diseases, however, the exact timing of these processes is unknown. Mitochondrial malfunction has a multitude of negative repercussions, including reduced calcium buffering and secondary excitotoxicity contributing to synaptic dysfunction, also free radical production, and activation of the mitochondrial permeability transition. Hence mitochondria are considered a therapeutic target in neurodegenerative disorders such as Alzheimer's. Traditional medicinal systems practiced in different countries employing various medicinal plants postulated to have potential role in the therapy and management of memory impairment including amnesia, dementia as well as AD. Although, the preclinical and clinical studies using these medicinal plants or plant products have demonstrated the therapeutic efficacy for AD, the precise mechanism of action is still obscure. Therefore, this review discusses the contribution of mitochondria towards AD pathogenesis and considering phytotherapeutics as a potential therapeutic strategy.
Access this article: https://doi.org/10.1016/j.mito.2024.101868
Title: Characterization of brain resilience in Alzheimer's disease using polygenic risk scores and further improvement by integrating mitochondria-associated loci
Authors: Xuan Xu, Hui Wang, David A. Bennett, Qing-Ye Zhang, Xiang-Yu Meng, Hong-Yu Zhang
Type: Research Article
Abstract:
Introduction
Identification of high-risk people for Alzheimer's disease (AD) is critical for prognosis and early management. Longitudinal epidemiologic studies have observed heterogeneity in the brain and cognitive aging. Brain resilience was described as above-expected cognitive function. The “resilience” framework has been shown to correlate with individual characteristics such as genetic factors and age. Besides, accumulative evidence has confirmed the association of mitochondria with the pathogenesis of AD. However, it is challenging to assess resilience through genetic metrics, in particular incorporating mitochondria-associated loci.
Objectives
In this paper, we first demonstrated that polygenic risk scores (PRS) could characterize individuals' resilience levels. Then, we indicated that mitochondria-associated loci could improve the performance of PRSs, providing more reliable measurements for the prevention and diagnosis of AD.
Methods
The discovery (N = 1,550) and independent validation samples (N = 2,090) were used to construct nine types of PRSs containing mitochondria-related loci (PRSMT) from both biological and statistical aspects and combined them with known AD risk loci derived from genome-wide association studies (GWAS). Individuals' levels of brain resilience were comprehensively measured by linear regression models using eight pathological characteristics.
Result
It was found that PRSs could characterize brain resilience levels (e.g., Pearson correlation test Pmin = 7.96×10-9). Moreover, the performance of PRS models could be efficiently improved by incorporating a small number of mitochondria-related loci (e.g., Pearson correlation test P improved from 1.41×10-3 to 6.09×10-6). PRSs' ability to characterize brain resilience was validated. More importantly, by incorporating some mitochondria-related loci, the performance of PRSs in measuring brain resilience could be significantly improved.
Conclusion
Our findings imply that mitochondria may play an important role in brain resilience, and targeting mitochondria may open a new door to AD prevention and therapy.
Access this article: https://doi.org/10.1016/j.jare.2023.03.002
