Depressive symptoms, anxiety and cognitive impairment: emerging evidence in multiple sclerosis DOI Creative Commons
Monica Margoni, Paolo Preziosa, Maria A. Rocca

et al.

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: July 19, 2023

Abstract Neuropsychiatric abnormalities may be broadly divided in two categories: disorders of mood, affect, and behavior affecting cognition. Among these conditions, clinical depression, anxiety neurocognitive are the most common multiple sclerosis (MS), with a substantial impact on patients’ quality life adherence to treatments. Such manifestations occur from earliest phases disease but become more frequent MS patients progressive course severe disability. Although pathogenesis neuropsychiatric has not been fully defined yet, brain structural functional abnormalities, consistently observed magnetic resonance imaging (MRI), together genetic immunologic factors, have suggested key players. Even though detrimental such is matter crucial importance, at present, they often overlooked setting. Moreover, efficacy pharmacologic non-pharmacologic approaches for their amelioration poorly investigated, majority studies showing marginal or no beneficial effect different therapeutic approaches, possibly due presence heterogeneous underlying pathological mechanisms intrinsic methodological limitations. A better evaluation setting improvements understanding pathophysiology offer potential develop tools differentiating individual ultimately provide principled basis treatment selection. This review provides an updated overview regarding symptoms MS, MRI characteristics that associated mood (i.e., depression anxiety) cognitive impairment, currently available under investigation.

Language: Английский

Hallmarks of neurodegenerative diseases DOI Creative Commons

David M. Wilson,

Mark Cookson, Ludo Van Den Bosch

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(4), P. 693 - 714

Published: Feb. 1, 2023

Summary

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks NDD: pathological protein aggregation, synaptic neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, cell death. describe hallmarks, their biomarkers, interactions as a framework to study NDDs using holistic approach. The can serve basis defining pathogenic mechanisms, categorizing different based on primary stratifying patients within specific NDD, designing multi-targeted, personalized therapies effectively halt NDDs.

Language: Английский

Citations

801
Astrocyte Crosstalk in CNS Inflammation DOI Creative Commons
Mathias Linnerbauer, Michael A. Wheeler, Francisco J. Quintana

et al.

Neuron, Journal Year: 2020, Volume and Issue: 108(4), P. 608 - 622

Published: Sept. 7, 2020

Language: Английский

Citations

661
Function and therapeutic value of astrocytes in neurological diseases DOI
Hong‐Gyun Lee, Michael A. Wheeler, Francisco J. Quintana

et al.

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(5), P. 339 - 358

Published: Feb. 16, 2022

Language: Английский

Citations

364
Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation DOI
Marco Prinz, Takahiro Masuda, Michael A. Wheeler

et al.

Annual Review of Immunology, Journal Year: 2021, Volume and Issue: 39(1), P. 251 - 277

Published: Feb. 9, 2021

The immune system of the central nervous (CNS) consists primarily innate cells. These are highly specialized macrophages found either in parenchyma, called microglia, or at CNS interfaces, such as leptomeningeal, perivascular, and choroid plexus macrophages. While they were thought phagocytes, their function extends well beyond simple removal cell debris during development diseases. Brain-resident cells to be plastic, long-lived, host an outstanding number risk genes for multiple pathologies. As a result, now considered most suitable targets modulating Additionally, recent single-cell technologies enhanced our molecular understanding origins, fates, interactomes, functional statesduring health perturbation. Here, we review current state challenges myeloid biology treatment options related

Language: Английский

Citations

353
Immune cell regulation of glia during CNS injury and disease DOI
Andrew D. Greenhalgh,

Sam David,

F. Chris Bennett

et al.

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(3), P. 139 - 152

Published: Feb. 10, 2020

Language: Английский

Citations

307
B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers DOI Creative Commons
Jamie van Langelaar, Liza Rijvers, Joost Smolders

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: May 8, 2020

Historically, multiple sclerosis (MS) has been viewed as being primarily driven by T cells. However, the effective use of anti-CD20 treatment now also reveals an important role for B cells in MS patients. The results from this put forward T-cell activation rather than antibody production a driving force behind MS. main question how their interaction provokes both and to infiltrate CNS cause local pathology remains be answered. In review, we highlight key pathogenic events involving that most likely contribute pathogenesis These include 1) peripheral escape cell-mediated control, 2) secondary lymph nodes, 3) reactivation accumulating CNS. We will focus on functional programs CNS-infiltrating lymphocyte subsets patients discuss these are defined mechanisms such antigen presentation, co-stimulation cytokine periphery. Furthermore, potential impact genetic variants viral triggers candidate debated context

Language: Английский

Citations

229
Clinical applications of stem cell-derived exosomes DOI Creative Commons
Fei Tan, Xuran Li, Zhao Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 12, 2024

Abstract Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery, it nevertheless comes with inescapable drawbacks that might limit its clinical translation. Compared cells, cell-derived exosomes possess numerous advantages, such as non-immunogenicity, non-infusion toxicity, easy access, effortless preservation, and freedom from tumorigenic ethical issues. Exosomes can inherit similar therapeutic effects their parental cells embryonic adult through vertical delivery of pluripotency or multipotency. After a thorough search meticulous dissection relevant literature the last five years, we present this comprehensive, up-to-date, specialty-specific disease-oriented review highlight surgical application exosomes. derived (e.g., embryonic, induced pluripotent, hematopoietic, mesenchymal, neural, endothelial cells) are capable treating encountered in orthopedic neurosurgery, plastic general cardiothoracic urology, head neck ophthalmology, obstetrics gynecology. The diverse cells-derived hierarchical translation tissue-specific responses, cell-specific molecular signaling pathways. In review, viable potent alternative managing various conditions. We recommend future research combines wisdoms surgeons, nanomedicine practitioners, cell researchers intriguing area.

Language: Английский

Citations

216
Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid DOI Creative Commons
Michael Heming, Xiaolin Li, Saskia Räuber

et al.

Immunity, Journal Year: 2020, Volume and Issue: 54(1), P. 164 - 175.e6

Published: Dec. 23, 2020

Language: Английский

Citations

159
Rituximab for the treatment of multiple sclerosis: a review DOI Open Access
Clara Grazia Chisari,

Eleonora Sgarlata,

Sebastiano Arena

et al.

Journal of Neurology, Journal Year: 2021, Volume and Issue: 269(1), P. 159 - 183

Published: Jan. 8, 2021

Language: Английский

Citations

154
Glymphatic system impairment in multiple sclerosis: relation with brain damage and disability DOI Open Access
Antonio Carotenuto, Laura Cacciaguerra, Elisabetta Pagani

et al.

Brain, Journal Year: 2021, Volume and Issue: 145(8), P. 2785 - 2795

Published: Dec. 13, 2021

Recent evidence has shown the existence of a CNS 'waste clearance' system, defined as glymphatic system. Glymphatic abnormalities have been described in several neurodegenerative conditions, including Alzheimer's and Parkinson's disease. function not thoroughly explored multiple sclerosis, where processes are intermingled with inflammatory processes. We aimed to investigate system sclerosis evaluate its association clinical disability, disease course, demyelination neurodegeneration, quantified using different MRI techniques. In this retrospective study, we enrolled 71 patients (49 relapsing-remitting 22 progressive sclerosis) 32 age- sex-matched healthy control subjects. All subjects underwent neurological assessment high-resolution T1, T2 double inversion recovery sequences, diffusion susceptibility weighted imaging. calculated along perivascular space index, proxy for function, cortical deep grey matter volume, white lesion volume normal-appearing microstructural damage. Multiple showed an overall lower index versus controls (estimated mean difference: -0.09, P = 0.01). Both had -0.06, 0.04 -0.19, 0.001 patients). Progressive 0.03). patients, was associated more severe disability (r -0.45, 0.001) longer duration -0.37, 0.002). Interestingly, detected negative between first 4.13 years course -0.38, 0.04) without any thereafter (up 34 duration). Lower higher -0.36, 0.003) -0.41, 0.30, 0.007) 0.42, atrophy, reduced fractional anisotropy increased diffusivity matter. Our results suggest that is impaired especially stages. Impaired measures both neurodegeneration reflects disability. These findings impairment may be pathological mechanism underpinning sclerosis. The dynamic interplay other substrates deserves further investigation.

Language: Английский

Citations

151