The Latest Articles on Ageing and Neurodegenerative Diseases

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

This week, we would like to share several of the latest articles on Ageing and Neurodegenerative Diseases.

Title: Role of Nrf2 in aging, Alzheimer’s and other neurodegenerative diseases
Authors: Mathew George, MatthanTharakan, JohnCulberson, Arubala P.Reddy, P. HemachandraReddy
Type: Review
Abstract:
Nuclear Factor-Erythroid Factor 2 (Nrf2) is an important transcription factor that regulates the expression of large number of genes in healthy and disease states. Nrf2 is made up of 605 amino acids and contains 7 conserved regions known as Nrf2-ECH homology domains. Nrf2 regulates the expression of several key components of oxidative stress, mitochondrial biogenesis, mitophagy, autophagy and mitochondrial function in all organs of the human body, in the peripheral and central nervous systems. Mounting evidence also suggests that altered expression of Nrf2 is largely involved in aging, neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s diseases, Amyotrophic lateral sclerosis, Stroke, Multiple sclerosis and others. The purpose of this article is to detail the essential role of Nrf2 in oxidative stress, antioxidative defense, detoxification, inflammatory responses, transcription factors, proteasomal and autophagic/mitophagic degradation, and metabolism in aging and neurodegenerative diseases. This article also highlights the Nrf2 structural and functional activities in healthy and disease states, and also discusses the current status of Nrf2 research and therapeutic strategies to treat aging and neurodegenerative diseases.
Access this article: https://doi.org/10.1016/j.arr.2022.101756

Title: Oligonucleotides: A novel area of interest for drug delivery in neurodegenerative diseases
Authors: Khalid Saad Alharbi, Mohammad Arshad Javed Shaikh, Obaid Afzal, Abdulmalik Saleh Alfawaz Altamimi, Waleed Hassan almalki, Imran Kazmi, Fahad A. Al-Abbasi, Sami I.Alzarea, M Ravindra Babu, Sachin Kumar Singh, Dinesh Kumar Chellappan, Kamal Duag, Gaurav Gupta
Type: Review
Abstract:
Several neurodegenerative diseases, such as AD, PD, and HD are characterized by the malfunction and deposition of a particular protein. Treatments for these diseases have typically sought to alleviate the downstream effects of protein malfunction, but it appears most rational to target the source of that dysfunction, the afflicted protein itself, to obtain a very effective treatment outcome. Treatment of neurodegenerative diseases using a segment of RNA or oligonucleotides has become popular. Thanks to groundbreaking discoveries during the past decade, RNA has played an increasingly important role in human health and disease. Therefore, therapeutic regulation of RNA function must be developed as RNA becomes a more important target. Several RNA-targeting oligonucleotides can be used, including aptamers, ASOs, siRNAs, and miRNAs. The development of oligonucleotides in this area of research has been made possible by technological developments. A neurodegenerative illness could be halted or prevented if oligonucleotides attach to these linked target proteins and inhibit their buildup. This article focuses on oligonucleotide and its uses in neurodegenerative illnesses such as AD, PD, and HD.
Access this article: https://doi.org/10.1016/j.jddst.2022.103849

Title: Daphne genkwa flower extract promotes the neuroprotective effects of microglia
Authors: Deepak Prasad Gupta, Sung Hee Park, Young-Sun Lee, Sanghyun Lee, Sujin Lim, Jiin Byun, Ik-Hyun Cho, Gyun Jee Song
Type: Original Article
Abstract:
Background
Microglia are innate immune cells in the central nervous system that play a crucial role in neuroprotection by releasing neurotrophic factors, removing pathogens through phagocytosis, and regulating brain homeostasis. The constituents extracted from the roots and stems of the Daphne genkwa plant have shown neuroprotective effects in an animal model of Parkinson's disease. However, the effect of Daphne genkwa plant extract on microglia has yet to be demonstrated.
Purpose
To study the anti-inflammatory and neuroprotective effects of Daphne genkwa flower extract (GFE) in microglia and explore the underlying mechanisms.
Methods
In-vitro mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase, Arginase1, and brain derived neurotropic factor (BDNF) were analyzed by reverse transcription polymerase chain reaction in microglia cells. Nitric oxide (NO) and TNF-α protein were respectively analyzed by Griess reagent and Enzyme Linked Immunosorbent Assay. Immunoreactivity of Iba-1, Neu-N, and BDNF in mouse brain were analyzed by immunofluorescence staining. Phagocytosis capacity of microglia was examined using fluorescent zymosan-red particles.
Results
GFE significantly inhibited lipopolysaccharide (LPS)-induced neuroinflammation and promoted neuroprotection both in vitro and in vivo. First, GFE inhibited the LPS-induced inflammatory factors NO, iNOS, and TNF-α in microglial cell lines and primary glial cells, thus demonstrating anti-inflammatory effects. Arginase1 and BDNF mRNA levels were increased in primary glial cells treated with GFE. Phagocytosis was also increased in microglia treated with GFE, suggesting a neuroprotective effect of GFE. In vivo, neuroprotective and anti-neuroinflammatory effects of GFE were also found in the mouse brain, as oral administration of GFE significantly inhibited LPS-induced neuronal loss and inflammatory activation of microglia.
Conclusion
GFE has anti-inflammatory effects and promotes microglial neuroprotective effects. GFE inhibited the pro-inflammatory mediators and enhanced neuroprotective microglia activity by increasing BDNF expression and phagocytosis. These novel findings of the GFE effect on microglia show an innovative approach that can potentially promote neuroprotection for the prevention of neurodegenerative diseases.
Access this article: https://doi.org/10.1016/j.phymed.2022.154486

Title: Targeting epigenetics as a promising therapeutic strategy for treatment of neurodegenerative diseases
Authors: Lan Zhang, Yi Liua, Yingying Lu, Guan Wang
Type: Review
Abstract:
Nowadays, epigenetics is of great research value as a new gateway that can solve the sophisticated mysteries behind neurodegenerative diseases. Epigenetic mechanisms, including DNA methylation, various post-translational modifications of histones, chromatin remodeling enzymes, and long non-coding RNAs, are robust modulators of gene expression levels. Over the past years, epigenetic processes have emerged as important factors in many neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Huntington’s disease. Here, we review the diverse types of epigenetic modifications and how these mechanisms become dysregulated across the lifespan. We then discuss the various promising strategies for the treatment of neurodegenerative diseases targeting epigenetics, paving the way for the development of novel treatment strategies in neurodegenerative diseases.
Access this article: https://doi.org/10.1016/j.bcp.2022.115295

Title: Benefits of Tai Chi Quan on neurodegenerative diseases: A systematic review
Authors: RuiWang, HaoZhou, Yu-Chen Wang, Xiao-Long Chang, Xue-Qiang Wang
Type: Review
Abstract:
Background
Neurodegenerative diseases have become an important concern with the accelerated aging process. Tai Chi Quan (TCQ) has positive benefits for brain health and chronic diseases. The aim of this study was to summarize the protective effects of TCQ for motor function, cognition, quality of life, and mood in patients with neurodegenerative diseases.
Methods
A systematic search was conducted via PubMed database and the Web of Science core collection database until August 20, 2021. The available English systematic reviews, meta-analyses, and clinical trials were included. Two reviewers completed the screening and assessment process independently.
Results
A total of 28 studies on Parkinson's disease, 21 on cognitive impairment, and 9 on multiple sclerosis met the included criteria. The study found that TCQ remarkably improved general motor function and balance, and prevented falls for Parkinson's disease. TCQ significantly improved global cognitive function for cognitive impairment. TCQ was likely safe and beneficial for multiple sclerosis as result of heterogeneous outcomes and small samples.
Conclusion
TCQ exercise can effectively improve the motor function, global cognitive function, and falls in patients with neurodegenerative diseases. However, the positive effects of TCQ on the quality of life and mood of patients with neurodegenerative diseases need further evidence.
Access this article: https://doi.org/10.1016/j.arr.2022.101741