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Editor's Recommended Articles

Published on: 4 Mar 2022 Viewed: 221

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

Title: Involvement of neuronal and muscular Trk-fused gene (TFG) defects in the development of neurodegenerative diseases
Authors: Takeshi Yamamotoya, Shun Hasei, Yasuyuki Akasaka, Yukino Ohata, Yusuke Nakatsu, Machi Kanna, Midori Fujishiro, Hideyuki Sakoda, Hiraku Ono, Akifumi Kushiyama, Hidemi Misawa, Tomoichiro Asano
Type: Article of Scientific Reports
Abstract:
Trk-fused gene (TFG) mutations have been identified in patients with several neurodegenerative diseases. In this study, we attempted to clarify the effects of TFG deletions in motor neurons and in muscle fibers, using tissue-specific TFG knockout (vMNTFG KO and MUSTFG KO) mice. vMNTFG KO, generated by crossing TFG floxed with VAChT-Cre, showed deterioration of motor function and muscle atrophy especially in slow-twitch soleus muscle, in line with the predominant Cre expression in slow-twitch fatigue-resistant (S) and fast-twitch fatigue-resistant (FR) motor neurons. Consistently, denervation of the neuromuscular junction (NMJ) was apparent in the soleus, but not in the extensor digitorum longus, muscle. Muscle TFG expressions were significantly downregulated in vMNTFG KO, presumably due to decreased muscle IGF-1 concentrations. However, interestingly, MUSTFG KO mice showed no apparent impairment of muscle movements, though a denervation marker, AChRγ, was elevated and Agrin-induced AChR clustering in C2C12 myotubes was inhibited. Our results clarify that loss of motor neuron TFG is sufficient for the occurrence of NMJ degeneration and muscle atrophy, though lack of muscle TFG may exert an additional effect. Reduced muscle TFG, also observed in aged mice, might be involved in age-related NMJ degeneration, and this issue merits further study. 
Access this article: https://doi.org/10.1038/s41598-022-05884-7


Title: Significance of mitochondrial activity in neurogenesis and neurodegenerative diseases
Authors: Serra Ozgen, Judith Krigman, Ruohan Zhang, Nuo Sun
Type: Review of Neural Regeneration Research
Abstract:
Mitochondria play a multidimensional role in the function and the vitality of the neurological system. From the generation of neural stem cells to the maintenance of neurons and their ultimate demise, mitochondria play a critical role in regulating our neural pathways’ homeostasis, a task that is critical to our cognitive health and neurological well-being. Mitochondria provide energy via oxidative phosphorylation for the neurotransmission and generation of an action potential along the neuron’s axon. This paper will first review and examine the molecular subtleties of the mitochondria’s role in neurogenesis and neuron vitality, as well as outlining the impact of defective mitochondria in neural aging. The authors will then summarize neurodegenerative diseases related to either neurogenesis or homeostatic dysfunction. Because of the significant detriment neurodegenerative diseases have on the quality of life, it is essential to understand their etiology and ongoing molecular mechanics. The mitochondrial role in neurogenesis and neuron vitality is essential. Dissecting and understanding this organelle’s role in the genesis and homeostasis of neurons should assist in finding pharmaceutical targets for neurodegenerative diseases.
Access this article: https://doi.org/10.4103/1673-5374.322429


Title: Progranulin as a therapeutic target in neurodegenerative diseases
Authors: Herve Rhinn, Nadine Tatton, Stella McCaughey, Michael Kurnellas, Arnon Rosenthal  
Type: Review of Trends in Pharmacological Sciences
Highlights:
●Progranulin (PGRN) is a secreted, immune regulatory protein produced by myeloid cells and some neurons that regulates lysosomal function, neuronal survival, and inflammation.
●GRN loss-of-function mutations cause neuronal ceroid lipofuscinosis and frontotemporal dementia-GRN (FTD-GRN) in a dosage-dependent manner.
●Mutations that reduce PGRN levels are also associated with higher risk for amyotrophic lateral sclerosis (ALS) and FTD caused by the hexanucleotide repeat expansion in the C9orf72 gene, Parkinson’s disease (PD), Alzheimer’s disease (AD), limbic-predominant age-related transactivation response DNA-binding protein 43 (TDP-43) encephalopathy, Gaucher disease, and autism.
●PGRN overexpression is protective in animal models for AD, PD, FTD, ALS, stroke, Gaucher disease, and arthritis.
●PGRN is being investigated as a therapeutic target for neurodegenerative diseases through multiple mechanisms of action.
Access this article: https://doi.org/10.1016/j.tips.2021.11.015


Title: White matter-associated microglia: New players in brain aging and neurodegenerative diseases
Authors: Kyusik Ahn, Seung-Jae Lee, Inhee Mook-Jung
Type: Review of Ageing Research Reviews
Highlights:
White matter aging is important for brain aging, but it is less identified.
●Specific form of microglia was observed in aged white matter, named WAM.
●Senescent WAM could cause white matter aging.
●Repopulation of microglia has neuroprotective potential.
●Recovery of senescent WAM could rejuvenate aged brain.
Abstract:
There has been growing interest in brain aging and rejuvenation. It is well known that brain aging is one of the leading causes of neurodegenerative diseases, such as Alzheimer’s disease, but brain aging alone can cause cognitive decline. Microglia are thought to act as ‘conductors’ of white matter aging by modulating diverse glial cells and phagocytosing white matter-derived myelin debris. A recent study identified a specific subpopulation of microglia in the white matter of aged mice, termed white matter-associated microglia (WAM). Additionally, senescent microglia show impaired phagocytic function and altered lipid metabolism, which cause accumulation of lipid metabolites and eventually lead to myelin sheath degeneration. These results suggest that senescent WAM could be pivotal players in axonal loss during brain aging. The aim of this review is to assess the current state of knowledge on brain aging, with an emphasis on the roles of the white matter and microglia, and suggest potential approaches for rejuvenating the aged brain.
Access this article: https://doi.org/10.1016/j.arr.2022.101574


Title: Heart rate variability in relation to cognition and behavior in neurodegenerative diseases: A systematic review and meta-analysis
Authors: Kathy Y.Liu, Thomas Elliott, Melanie Knowles, Robert Howard
Type: Review of Ageing Research Reviews
Highlights:
Heart rate variability is proposed to be influenced by a neural network involved in autonomic regulation.
●Neurodegenerative processes alter the integrity of the central autonomic network.
●We reviewed studies of HRV and cognition/behavior in neurodegenerative diseases.
●We found a moderate correlation between HRV and measures of cognition/behavior.
Abstract:
Neurodegenerative diseases, which frequently present with neuropsychiatric symptoms related to prefrontal cortical dysfunction, can alter the integrity of the neural networks involved in central autonomic nervous system regulation, which is proposed to be indexed by heart rate variability (HRV). We systematically reviewed the characteristics, methodology and outcomes of 27 studies of HRV in relation to measures of cognition and behavior in neurodegenerative conditions, and assessed the strength of this relationship, cross-sectionally, across 18 studies. A significant, moderate effect was observed (r = 0.25), such that higher HRV was related to better cognitive and behavioral scores, which was not influenced by mean age or cognitive status. There was no evidence of small-study effects but we could not rule out publication bias, and other factors may have contributed to heterogeneity between studies. Our findings support the proposal that HRV may be a marker of self-regulatory processes in neurodegenerative conditions, and further research on this association is needed in relation to neuropsychiatric symptoms and alongside neuroimaging methods.
Access this article: https://doi.org/10.1016/j.arr.2021.101539


Title: Mitochondrial dysfunctions in neurodegenerative diseases: role in disease pathogenesis, strategies for analysis and therapeutic prospects
Authors: Federica Rey, Sara Ottolenghi, Gian Vincenzo Zuccotti, Michele Samaja, Stephana Carelli
Type: Review of Neural Regeneration Research
Abstract:
Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes, the mitochondria are required for multiple pivotal processes that include the production of biological energy, the biosynthesis of reactive oxygen species, the control of calcium homeostasis, and the triggering of cell death. The disruption of anyone of these processes has been shown to impact strongly the function of all cells, but especially of neurons. In this review, we discuss the role of the mitochondria impairment in the development of the neurodegenerative diseases Amyotrophic Lateral Sclerosis, Parkinson’s disease and Alzheimer’s disease. We highlight how mitochondria disruption revolves around the processes that underlie the mitochondria’s life cycle: fusion, fission, production of reactive oxygen species and energy failure. Both genetic and sporadic forms of neurodegenerative diseases are unavoidably accompanied with and often caused by the dysfunction in one or more of the key mitochondrial processes. Therefore, in order to get in depth insights into their health status in neurodegenerative diseases, we need to focus into innovative strategies aimed at characterizing the various mitochondrial processes. Current techniques include Mitostress, Mitotracker, transmission electron microscopy, oxidative stress assays along with expression measurement of the proteins that maintain the mitochondrial health. We will also discuss a panel of approaches aimed at mitigating the mitochondrial dysfunction. These include canonical drugs, natural compounds, supplements, lifestyle interventions and innovative approaches as mitochondria transplantation and gene therapy. In conclusion, because mitochondria are fundamental organelles necessary for virtually all the cell functions and are severely impaired in neurodegenerative diseases, it is critical to develop novel methods to measure the mitochondrial state, and novel therapeutic strategies aimed at improving their health.
Access this article: https://doi.org/10.4103/1673-5374.322430

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