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Recommended articles of this week

Published on: 23 Mar 2022 Viewed: 408

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 from our editorial board of the journal Ageing and Neurodegenerative Diseases.

Title: The different autophagy degradation pathways and neurodegeneration
Authors: AngeleenFleming,Mathieu Bourdenx,Motoki Fujimaki,Cansu Karabiyik,Gregory J. Krause,Ana Lopez,Adrián Martín-Segura,Claudia Puri,Aurora Scrivo,John Skidmore,Sung Min Son,Eleanna Stamatakou,Lidia Wrobel,Ye Zhu,Ana Maria Cuervo,David C. Rubinsztein
Type: Review
Summary:
The term autophagy encompasses different pathways that route cytoplasmic material to lysosomes for degradation and includes macroautophagy, chaperone-mediated autophagy, and microautophagy. Since these pathways are crucial for degradation of aggregate-prone proteins and dysfunctional organelles such as mitochondria, they help to maintain cellular homeostasis. As post-mitotic neurons cannot dilute unwanted protein and organelle accumulation by cell division, the nervous system is particularly dependent on autophagic pathways. This dependence may be a vulnerability as people age and these processes become less effective in the brain. Here, we will review how the different autophagic pathways may protect against neurodegeneration, giving examples of both polygenic and monogenic diseases. We have considered how autophagy may have roles in normal CNS functions and the relationships between these degradative pathways and different types of programmed cell death. Finally, we will provide an overview of recently described strategies for upregulating autophagic pathways for therapeutic purposes.
Access this article: https://doi.org/10.1016/j.neuron.2022.01.017


Title: The MDS consensus tremor classification: The best way to classify patients with tremor at present
Authors: Anna Latorre, Mark Hallett, Günther Deuschl, Kailash P. Bhatia
Type: Review Article
Highlights:
●In 2018, the new Consensus Statement on the Classification of Tremors was published.
●Tremor is classified according to clinical manifestation and etiology (Axis 1 and 2).
●Essential tremor is considered as a syndrome.
●The new category essential tremor plus is recognised.
●Considering our current knowledge, this tremor classification is the best at present.
Abstract:
In 2018, the new Consensus Statement on the Classification of Tremors, by the Task Force on Tremor of the International Parkinson Movement Disorder Society, was published. So far, the article has been cited more than 400 times in peer-reviewed international journals and commonly debated in conferences and meetings due to an enthusiastic welcome from the community.
Compared to the previous Consensus Statement (1998), the main novelties are: 1) the classification of tremor according to clinical manifestation (Axis 1) and etiology (Axis 2), and therefore the use of a syndromic approach; 2) the definition of essential tremor as a syndrome; 3) the recognition of the new category essential tremor plus, that derives from the uncertain significance of the soft neurological signs often associated with essential tremor.
In this paper, we summarise and explain the most important aspects of the new classification of tremors, highlighting the main novelties, their relevance, and application in clinical practice. Moreover, we discuss its possible weakness and reflect on the critical comments made so far.
We believe that this new tremor classification is comprehensive, rigorous, and consistent and, considering our current knowledge of tremor syndromes, it is the best we can do at present.
Access this article: https://doi.org/10.1016/j.jns.2022.120191


Title: What's in the Sauce? The Specific Benefits of Palliative Care for Parkinson's Disease
Authors: Meredith Bock, Maya Katz, Stefan Sillau, Kwame Adjepong, Kristine Yaffe, Roman Ayele, Zachary A. Macchi, Steven Pantilat, Janis M. Miyasaki, Benzi Kluger
Type: Original Article
Abstract:
Context
Increasing evidence demonstrates the benefits of palliative care among individuals with Parkinson's disease and related disorders (PDRD), but the critical components that contribute to therapeutic effects are not well understood.
Objectives
To determine the specific items most responsive to a palliative care intervention in PDRD and identify key correlates of improvement in patient and care partner outcomes.
Methods
The main trial was a pragmatic comparative effectiveness trial of outpatient integrated palliative care compared to standard care among participants with PDRD (NCT02533921), showing significantly higher patient QOL at six months and lower care partner burden at 12 months. We used longitudinal regression models to analyze changes in subdomains of patient QOL and care partner burden and Spearman correlations to evaluate key correlates of change scores in patient and care partner outcomes. We performed a secondary analysis of data from 210 patients and 175 care partners.
Results
Compared to controls, patients in the intervention reported greater improvement in perceptions of the “self as a whole” at six months (coeff = 0.22, P < 0.05) and care partners reported greater reduction in stress, anger, and loss of control at 12 months (coeff = -.40, -0.25, -0.31, P < 0.05). Positive change in numerous patient non-motor symptoms and grief correlated with improved patient QOL, reduced patient anxiety, and increased care partner spirituality. Alleviation of care partner anxiety and depression correlated with reduced care partner burden.
Conclusion
Specific benefits of an integrated palliative approach in PDRD include improvement in patient holistic self-impressions, care partner self-efficacy, and non-motor symptoms.
Access this article: https://doi.org/10.1016/j.jpainsymman.2022.01.017


Title: Activation of autophagy attenuates motor deficits and extends lifespan in a C. elegans model of ALS
Authors: Hui Xu, Congcong Jia, Cheng Cheng, Haifeng Wu, Huaibin Cai, Weidong Le
Type: Research Article
Highlights:
●hSOD1G93A induces motor neuron degeneration and shortens the lifespan in ALS C. elegans.
●Metformin alleviates motor dysfunction and extends lifespan in ALS worms.
●Metformin activates autophagy and daf-16 pathways.
Abstract:
Mutations in Cu/Zn–superoxide dismutase 1 (SOD1) are linked to amyotrophic lateral sclerosis (ALS). Using a line of ALS-related mutant human SOD1 (hSOD1) transgenic Caenorhabditis elegans, we determined the effects of metformin on the progression of ALS-like pathological abnormalities. We found that metformin significantly extended the lifespan, improved motor performance, and enhanced antioxidant activity of mutant worms. We further showed that metformin enhanced expression of lgg-1, daf-16, skn-1 and other genes known to regulate autophagy, longevity and oxidative stress in hSOD1 transgenic worms. Accordingly, overexpression of lgg-1 or daf-16 attenuated the aging and pathological abnormalities of mutant human SOD1 worms, while genetic deletion of lgg-1 or daf-16 abolished the beneficial effects of metformin. Collectively, we demonstrate that metformin protects against mutant SOD1-induced cytotoxicity in part through enhancement of autophagy and extends lifespan through daf-16 pathway. Our findings suggest that metformin could be further explored as a potential therapeutic agent in treating ALS.
Access this article: https://doi.org/10.1016/j.freeradbiomed.2022.01.030


Title: Translation of the poly(GR) frame in C9ORF72-ALS/FTD is regulated by cis-elements involved in alternative splicing
Authors: Alexa Lampasona, Sandra Almeida, Fen-Biao Gao
Type: Brief Communication
Highlights:
●Poly(GR) frame translation in C9ORF72-ALS/FTD reporter does not depend on repeats.
●Poly(GR) frame translation does not depend on CUG start codon required for poly(GA) synthesis.
●Poly(GR) frame translation is regulated by 5' cis elements involved in alternative splicing.
Abstract:
GGGGCC (G4C2) repeat expansion in the first intron of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia, two devastating age-dependent neurodegenerative disorders. Both sense and antisense repeat RNAs can be translated into 5 different dipeptide repeat proteins, such as poly(GR), which is toxic in various cellular and animal models. However, it remains unknown how poly(GR) is synthesized in patient neurons. Using a reporter construct containing 70 G4C2 repeats flanked by human intronic and exonic sequences, we show that translation of the poly(GR) frame does not depend on repeats or the CUG start codon in the poly(GA) frame, suggesting poly(GR) is not produced after ribosomal frameshifting in the poly(GA) frame. However, deletion analysis suggests that translation of the poly(GR) frame depends on the length of the intronic sequence 5' adjacent to G4C2 repeats. Moreover, several 5´ cis elements that are predicted to be involved in alternative splicing regulates poly(GR) synthesis. These results suggest that translation of repeat RNAs in the poly(GR) frame is regulated by multiple cis elements, likely through RNA secondary structures and/or associated RNA binding proteins
Access this article: https://doi.org/10.1016/j.neurobiolaging.2021.04.030


Title: Chapter 4 - Sleep and homeostatic control of plasticity
Authors: Giuseppe Lanza, Lourdes M. DelRosso, Raffaele Ferri
Type: Book Chapter
Abstract:
Sleep homeostasis is a complex neurobiologic phenomenon involving a number of molecular pathways, neurotransmitter release, synaptic activity, and factors modulating neural networks. Sleep plasticity allows for homeostatic optimization of neural networks and the replay-based consolidation of specific circuits, especially important for cognition, behavior, and information processing. Furthermore, research is currently moving from an essentially brain-focused to a more comprehensive view involving other systems, such as the immune system, hormonal status, and metabolic pathways. When dysfunctional, these systems contribute to sleep loss and fragmentation as well as to sleep need. In this chapter, the implications of neural plasticity and sleep homeostasis for the diagnosis and treatment of some major sleep disorders, such as insomnia and sleep deprivation, obstructive sleep apnea syndrome, restless legs syndrome, REM sleep behavior disorder, and narcolepsy are discussed in detail with their therapeutical implications. This chapter highlights that sleep is necessary for the maintenance of an optimal brain function and is sensitive to both genetic background and environmental enrichment. Even in pathologic conditions, sleep acts as a resilient plastic state that consolidates prior information and prioritizes network activity for efficient brain functioning.
Access this article: https://doi.org/10.1016/B978-0-12-819410-2.00004-7

Ageing and Neurodegenerative Diseases
ISSN 2769-5301 (Online)

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