scholarly journals She Doesn’t Even Go Here: The Role of Inflammatory Astrocytes in CNS Disorders

2021 ◽  
Vol 15 ◽  
Author(s):  
Jacqueline Kelsey Reid ◽  
Hedwich Fardau Kuipers
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Therapeutic Targeting ◽  
Future Directions ◽  
Cns Disorders ◽  
Disease Modifying Therapies ◽  
Astrocyte Heterogeneity ◽  
Disease Modifying ◽  
Innovative Techniques

Astrocyte heterogeneity is a rapidly evolving field driven by innovative techniques. Inflammatory astrocytes, one of the first described subtypes of reactive astrocytes, are present in a variety of neurodegenerative diseases and may play a role in their pathogenesis. Moreover, genetic and therapeutic targeting of these astrocytes ameliorates disease in several models, providing support for advancing the development of astrocyte-specific disease modifying therapies. This review aims to explore the methods and challenges of identifying inflammatory astrocytes, the role these astrocytes play in neurological disorders, and future directions in the field of astrocyte heterogeneity.

ATP-binding cassette transporters and neurodegenerative diseases

2021 ◽  
Author(s):  
Jared S. Katzeff ◽  
Woojin Scott Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Abc Transporters ◽  
Brain Diseases ◽  
Atp Binding ◽  
Future Directions ◽  
Diverse Range ◽  
The Brain ◽  
Lateral Sclerosis ◽  
Atp Binding Cassette

Abstract ATP-binding cassette (ABC) transporters are one of the largest groups of transporter families in humans. ABC transporters mediate the translocation of a diverse range of substrates across cellular membranes, including amino acids, nucleosides, lipids, sugars and xenobiotics. Neurodegenerative diseases are a group of brain diseases that detrimentally affect neurons and other brain cells and are usually associated with deposits of pathogenic proteins in the brain. Major neurodegenerative diseases include Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. ABC transporters are highly expressed in the brain and have been implicated in a number of pathological processes underlying neurodegenerative diseases. This review outlines the current understanding of the role of ABC transporters in neurodegenerative diseases, focusing on some of the most important pathways, and also suggests future directions for research in this field.

Patient Perceptions of FDA Approval: Gaps in Education or Variation in Values?

2021 ◽  
pp. 10.1212/CPJ.0000000000001034
Author(s):  
Paul J. Ford ◽  
Robert J. Fox ◽  
Mary Beth Mercer ◽  
Stacey S. Cofield
Keyword(s):  
Drug Approval ◽  
Patient Perceptions ◽  
Approval Process ◽  
Inclusion Criteria ◽  
Web Based ◽  
Risks And Benefits ◽  
Disease Modifying Therapies ◽  
Fda Approval ◽  
Disease Modifying

Abstract:Objective:To assess perceptions and opinions about the FDA approval process for disease modifying therapies (DMT) in people living with multiple sclerosis (MS).Methods:People living with MS were invited to complete a web-based survey of their perceptions of the FDA role and process for approval of MS medications. The survey asked about the role of the FDA, factors involved in the approval process, which voices should represent those with MS in deliberations about drug approval, and the level of comfort with uncertain safety of newly-approved therapies.Results:3533 respondents met inclusion criteria for data analysis. Most respondents appeared to understand the role of the FDA, although only half understood a fundamental FDA role: balancing the risks and benefits when considering drug approval. Significant differences were observed in many areas between those who have and have not tried DMTs. Comfort with uncertainty was associated with several factors relating to side effects and benefits thought important for the FDA to consider. Most respondents reported that people who participated in the medication’s clinical trial were particularly able to represent people living with MS.Conclusion:Perceptions regarding the FDA and views of who should represent people living with MS varied between those who have and have not tried DMT. There is variability in personal values that should be recognized and taken into account when considering regulatory responsibilities. Interventions are needed to address educational gaps regarding the mission and trustworthiness of the FDA as an oversight body.

scholarly journals Critical Appraisal of Amyloid Lowering Agents in AD

2021 ◽  
Vol 21 (8) ◽  
Author(s):  
Boris Decourt ◽  
Fadel Boumelhem ◽  
Evans D. Pope ◽  
Jiong Shi ◽  
Zoltan Mari ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Drug Approval ◽  
Final Decision ◽  
Valuable Insight ◽  
Future Directions ◽  
Avant Garde ◽  
Aβ Aggregation ◽  
Disease Modifying ◽  
Disease Modifying Agents ◽  
Amyloid Cascade

Abstract Purpose of Review According to the amyloid cascade hypothesis, removing amyloid beta (Aβ) should cure Alzheimer’s disease (AD). In the past three decades, many agents have been tested to try to lower Aβ production, prevent Aβ aggregation, and dissolve Aβ deposits. However, the paucity in definitive preventative or curative properties of these agents in clinical trials has resulted in more avant-garde approaches to therapeutic investigations. Immunotherapy has become an area of focus for research on disease-modifying therapies for neurodegenerative diseases. In this review, we highlight the current clinical development landscape of monoclonal antibody (mAb) therapies that target Aβ plaque formation and removal in AD. Recent Findings Multiple potential disease-modifying therapeutics for AD are in active development. Targeting Aβ with mAbs has the potential to treat various stages of AD: prodromal, prodromal to mild, mild, and mild to moderate. Monoclonal antibodies discussed here include aducanumab, lecanemab, solanezumab, crenezumab, donanemab, and gantenerumab. Summary The final decision by the FDA regarding the approval of aducanumab will offer valuable insight into the trajectory of drug development for mAbs in AD and other neurodegenerative diseases. Future directions for improving the treatment of AD will include more inquiry into the efficacy of mAbs as disease-modifying agents that specifically target Aβ peptides and/or multimers. In addition, a more robust trial design for AD immunotherapy agents should improve outcomes such that objective measures of clinical efficacy will eventually lead to higher chances of drug approval.

Translational research on disease-modifying therapies for neurodegenerative diseases

2013 ◽  
Vol 1 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Masahisa Katsuno ◽  
Hirohisa Watanabe ◽  
Fumiaki Tanaka ◽  
Gen Sobue
Keyword(s):  
Neurodegenerative Diseases ◽  
Translational Research ◽  
Disease Modifying Therapies ◽  
Disease Modifying

scholarly journals Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Wojciech Kozubski ◽  
Kevin Ong ◽  
Wioletta Waleszczyk ◽  
Matthew Zabel ◽  
Jolanta Dorszewska
Keyword(s):  
Synaptic Plasticity ◽  
Neurodegenerative Diseases ◽  
Learning And Memory ◽  
Neural Plasticity ◽  
Lewy Bodies ◽  
Brain Diseases ◽  
Memory And Learning ◽  
Disease Modifying Therapies ◽  
Disease Modifying

Neural plasticity—the ability to alter a neuronal response to environmental stimuli—is an important factor in learning and memory. Short-term synaptic plasticity and long-term synaptic plasticity, including long-term potentiation and long-term depression, are the most-characterized models of learning and memory at the molecular and cellular level. These processes are often disrupted by neurodegeneration-induced dementias. Alzheimer’s disease (AD) accounts for 50% of cases of dementia. Vascular dementia (VaD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) constitute much of the remaining cases. While vascular lesions are the principal cause of VaD, neurodegenerative processes have been established as etiological agents of many dementia diseases. Chief among such processes is the deposition of pathological protein aggregates in vivo including β-amyloid deposition in AD, the formation of neurofibrillary tangles in AD and FTD, and the accumulation of Lewy bodies composed of α-synuclein aggregates in DLB and PDD. The main symptoms of dementia are cognitive decline and memory and learning impairment. Nonetheless, accurate diagnoses of neurodegenerative diseases can be difficult due to overlapping clinical symptoms and the diverse locations of cortical lesions. Still, new neuroimaging and molecular biomarkers have improved clinicians’ diagnostic capabilities in the context of dementia and may lead to the development of more effective treatments. Both genetic and environmental factors may lead to the aggregation of pathological proteins and altered levels of cytokines, such that can trigger the formation of proinflammatory immunological phenotypes. This cascade of pathological changes provides fertile ground for the development of neural plasticity disorders and dementias. Available pharmacotherapy and disease-modifying therapies currently in clinical trials may modulate synaptic plasticity to mitigate the effects neuropathological changes have on cognitive function, memory, and learning. In this article, we review the neural plasticity changes seen in common neurodegenerative diseases from pathophysiological and clinical points of view and highlight potential molecular targets of disease-modifying therapies.

scholarly journals Metallothionein in Brain Disorders

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Daniel Juárez-Rebollar ◽  
Camilo Rios ◽  
Concepción Nava-Ruíz ◽  
Marisela Méndez-Armenta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Regulation Of Gene Expression ◽  
Main Function ◽  
Brain Disorders ◽  
Essential Metals ◽  
The Central Nervous System

Metallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I–IV), three of which have been localized in the central nervous system. MT-I and MT-II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT-III has been found mainly in neurons. MT-I and MT-II have been considered polyvalent proteins whose main function is to maintain cellular homeostasis of essential metals such as zinc and copper, but other functions have also been considered: detoxification of heavy metals, regulation of gene expression, processes of inflammation, and protection against free radicals generated by oxidative stress. On the other hand, the MT-III has been related in events of pathogenesis of neurodegenerative diseases such as Parkinson and Alzheimer. Likewise, the participation of MTs in other neurological disorders has also been reported. This review shows recent evidence about the role of MT in the central nervous system and its possible role in neurodegenerative diseases as well as in brain disorders.

scholarly journals Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Khushwant S. Bhullar ◽  
H. P. Vasantha Rupasinghe
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Drug Targets ◽  
Nutritional Intervention ◽  
Testable Hypothesis ◽  
Brain Physiology ◽  
Age Related ◽  
Therapeutic Outcomes ◽  
Polyphenol Intake

Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer’s disease (AD), stroke, multiple sclerosis (MS), Parkinson’s disease (PD), and Huntington’s disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders.

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