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1.
J Neuroinflammation ; 21(1): 97, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627787

RESUMO

The unfavorable prognosis of many neurological conditions could be attributed to limited tissue regeneration in central nervous system (CNS) and overwhelming inflammation, while liver X receptor (LXR) may regulate both processes due to its pivotal role in cholesterol metabolism and inflammatory response, and thus receives increasing attentions from neuroscientists and clinicians. Here, we summarize the signal transduction of LXR pathway, discuss the therapeutic potentials of LXR agonists based on preclinical data using different disease models, and analyze the dilemma and possible resolutions for clinical translation to encourage further investigations of LXR related therapies in CNS disorders.


Assuntos
Doenças do Sistema Nervoso Central , Receptores Nucleares Órfãos , Humanos , Receptores X do Fígado , Receptores Nucleares Órfãos/metabolismo , Sistema Nervoso Central/metabolismo , Inflamação , Doenças do Sistema Nervoso Central/tratamento farmacológico
2.
Neurotherapeutics ; 20(4): 1037-1054, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37084148

RESUMO

Niacin (vitamin B3) is an essential nutrient that treats pellagra, and prior to the advent of statins, niacin was commonly used to counter dyslipidemia. Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin, including its homeostatic roles in NAD+ supplementation and metabolism. Niacin also has roles outside of metabolism, largely through engaging hydroxycarboxylic acid receptor 2 (Hcar2). These receptor-mediated activities of niacin include regulation of immune responses, phagocytosis of myelin debris after demyelination or of amyloid beta in models of Alzheimer's disease, and cholesterol efflux from cells. We describe the neurological disorders in which niacin has been investigated or has been proposed as a candidate medication. These are multiple sclerosis, Alzheimer's disease, Parkinson's disease, glioblastoma and amyotrophic lateral sclerosis. Finally, we explore the proposed mechanisms through which niacin may ameliorate neuropathology. While several questions remain, the prospect of niacin as a therapeutic to alleviate neurological impairment is promising.


Assuntos
Doença de Alzheimer , Doenças do Sistema Nervoso , Neurologia , Niacina , Pelagra , Humanos , Niacina/uso terapêutico , Niacina/metabolismo , Peptídeos beta-Amiloides , Pelagra/metabolismo
3.
J Neuroimmunol ; 362: 577777, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34823122

RESUMO

Multiple sclerosis is an inflammatory and neurodegenerative condition that is frequently modeled using experimental autoimmune encephalomyelitis (EAE). Current methods of EAE histology include imprecise qualitative assessments and time-consuming analyses of selected regions. With increasing interest in neuroprotective or reparative therapies, it is important that potential therapeutics are evaluated in EAE through quantitative neuropathology. We describe a quantitative whole slide imaging immunofluorescence method that allows longitudinal sections of the entire EAE thoracic spinal cord to be investigated for the extent of neuroinflammation, axonal loss, and myelin density. This method should impact MS research by making histological comparisons of EAE increasingly robust.


Assuntos
Encefalomielite Autoimune Experimental/patologia , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência/métodos , Medula Espinal/patologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL
4.
Curr Opin Pharmacol ; 61: 120-126, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34688996

RESUMO

Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system. While remyelination facilitates functional recovery in animal models, it is limited in people with multiple sclerosis. Thus, multiple strategies have been put forth to promote remyelination, including exercise and medication. Exercise promotes the release of growth factors and induces protein-level changes, while remyelinating medications act through a variety of mechanisms to promote oligodendrocyte maturation within the lesion. In animal models, the combination of medication and exercise (Medication + eXercise = MedXercise) has an additive effect on remyelination and other pathological features of multiple sclerosis. In this review, we highlight the existing literature on the effects of exercise and medication on remyelination both independently and in combination.


Assuntos
Esclerose Múltipla , Remielinização , Animais , Sistema Nervoso Central , Modelos Animais de Doenças , Humanos , Esclerose Múltipla/tratamento farmacológico , Oligodendroglia , Recuperação de Função Fisiológica
5.
Cureus ; 13(6): e15972, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34336464

RESUMO

Despite the high prevalence of concussions each year in Canada, access to consistent and science-based information on how to self-manage these injuries remains a significant hurdle for many patients. Currently, available mobile applications (apps) focus mainly on supporting patients with sports-related concussions, although falls account for more traumatic brain injuries (TBI) than sports-related TBI's in Alberta. Patients from a broader demographic may be limited from accessing information on how to correctly manage and track their symptoms as they feel that currently available resources are not applicable to them. Through collaboration between health system leaders, expert consultations, patients, and university students, a mobile app was designed as a platform to help patients manage and track symptoms at home, as well as to clarify misleading information and misconceptions surrounding injury. The team engaged numerous physicians, patient advisors, and health system leaders to improve upon the features of currently-existing concussion apps such as symptom tracking, insight into concussion, and strategies for returning to work/school that are more inclusive to adult, non-sports related injuries. We believe that these features will advance recovery by alleviating the burden of uncertainty and confusion for patients and their family members.

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