Signaling inflammation across the gut-brain axis

Science, Journal Year: 2021, Volume and Issue: 374(6571), P. 1087 - 1092

Published: Nov. 25, 2021

The brain and gastrointestinal tract are critical sensory organs responsible for detecting, relaying, integrating, responding to signals derived from the internal external environment. At interface of this function, immune cells in intestines consistently survey environmental factors, eliciting responses that inform on physiological state body. Recent research reveals cross-talk along gut-brain axis regulates inflammatory nociception, responses, homeostasis. Here, we discuss molecular cellular mechanisms involved signaling inflammation across axis. We further highlight interactions between gut inflammation-associated diseases.

Language: Английский

---

Function and therapeutic value of astrocytes in neurological diseases

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

Published: Feb. 16, 2022

Language: Английский

---

The Immune Response in Multiple Sclerosis

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2021, Volume and Issue: 17(1), P. 121 - 139

Published: Oct. 4, 2021

Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative disease that affects the central nervous system (CNS). MS characterized by immune dysregulation, which results in infiltration of CNS cells, triggering demyelination, axonal damage, neurodegeneration. Although exact causes are not fully understood, genetic environmental factors thought to control onset progression. In this article, we review main immunological mechanisms involved pathogenesis.

Language: Английский

---

Neuroinflammation in Alzheimer’s Disease

Biomedicines, Journal Year: 2021, Volume and Issue: 9(5), P. 524 - 524

Published: May 7, 2021

Alzheimer's disease (AD) is a neurodegenerative associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise increasing age. There are currently no effective modifying treatments for AD, resulting in increasingly large socioeconomic personal costs. Increasing age an increase low-grade chronic inflammation (inflammaging) that may contribute the process AD. Although exact mechanisms remain unclear, aberrant elevation reactive oxygen nitrogen species (RONS) levels from several endogenous exogenous processes brain not only affect cell signaling, but also trigger cellular senescence, inflammation, pyroptosis. Moreover, compromised immune privilege allows infiltration peripheral cells infectious agents play role. Additionally, meta-inflammation as well gut microbiota dysbiosis drive neuroinflammatory process. Considering inflammatory/immune pathways dysregulated parallel cognitive dysfunction elucidating relationship between central nervous system facilitate development safe therapy We discuss some current ideas on inflammaging appear summarize details few immunomodulatory strategies being developed selectively target detrimental aspects neuroinflammation without affecting defense against pathogens tissue damage.

Language: Английский

---

Beyond the GFAP-Astrocyte Protein Markers in the Brain

Biomolecules, Journal Year: 2021, Volume and Issue: 11(9), P. 1361 - 1361

Published: Sept. 14, 2021

The idea of central nervous system as one-man band favoring neurons is long gone. Now we all are aware that and neuroglia team players constant communication between those various cell types essential to maintain functional efficiency a quick response danger. Here, summarize discuss known new markers astroglial multiple functions, their natural heterogeneity, cellular interactions, aging disease-induced dysfunctions. This review focused on newly reported facts regarding astrocytes, which beyond the old stereotypes. We present an up-to-date list marker proteins used identify broad spectrum phenotypes related physiological pathological conditions. aim this help choose well-tailored for specific needs further experimental studies, precisely recognizing differential glial phenotypes, or diagnostic purposes. hope it will categorize structural diversity population ease clear readout future results.

Language: Английский

---

Dopamine, Immunity, and Disease

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 75(1), P. 62 - 158

Published: Dec. 8, 2022

The neurotransmitter dopamine is a key factor in central nervous system (CNS) function, regulating many processes including reward, movement, and cognition. Dopamine also regulates critical functions peripheral organs, such as blood pressure, renal activity, intestinal motility. Beyond these functions, growing body of evidence indicates that an important immunoregulatory factor. Most types immune cells express receptors other dopaminergic proteins, take up, produce, store, and/or release dopamine, suggesting immunomodulation for function. Targeting pathways could be promising avenue the treatment inflammation disease, but despite increasing research this area, data on specific effects disease remain inconsistent poorly understood. Therefore, review integrates current knowledge role cell function inflammatory signaling across systems. We discuss understanding regulation CNS tissues, highlighting diseases Parkinson’s several neuropsychiatric conditions, neurologic human immunodeficiency virus, bowel rheumatoid arthritis, others. Careful consideration given to influence experimental design results, we note number areas need further research. Overall, our immunology at cellular, tissue, level prompts development therapeutics strategies targeted toward ameliorating through immunity.

Significance Statement

Canonically, recognized involved cognition, reward. However, acts modulator periphery. This comprehensively assesses pathogenesis cellular tissue level. will provide broad access information fields, identify investigation, drive therapeutic strategies.

Language: Английский

---

Innate Immune Cell Death in Neuroinflammation and Alzheimer’s Disease

Cells, Journal Year: 2022, Volume and Issue: 11(12), P. 1885 - 1885

Published: June 10, 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder molecularly characterized by the formation of amyloid β (Aβ) plaques and type 2 microtubule-associated protein (Tau) abnormalities. Multiple studies have shown that many brain’s immunological cells, specifically microglia astrocytes, are involved in AD pathogenesis. Cells innate immune system play an essential role eliminating pathogens but also regulate brain homeostasis AD. When activated, cells can cause programmed cell death through multiple pathways, including pyroptosis, apoptosis, necroptosis, PANoptosis. The often results release proinflammatory cytokines propagate response eliminate Aβ aggregated Tau proteins. However, chronic neuroinflammation, which result from death, has been linked to diseases worsen Therefore, must be tightly balanced appropriately clear these AD-related structural abnormalities without inducing neuroinflammation. In this review, we discuss responses, inflammatory cytokine secretion as they relate Therapeutic strategies targeting mechanisms will critical consider for future preventive or palliative treatments

Language: Английский

---

Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis

Neurology Neuroimmunology & Neuroinflammation, Journal Year: 2022, Volume and Issue: 10(1)

Published: Nov. 14, 2022

Neurodegeneration and astrocytic activation are pathologic hallmarks of progressive multiple sclerosis (MS) can be quantified by serum neurofilament light chain (sNfL) glial fibrillary acidic protein (sGFAP). We investigated sNfL sGFAP as tools for stratifying patients with MS based on progression disease activity status.We leveraged our Comprehensive Longitudinal Investigation at the Brigham Women's Hospital (CLIMB) natural history study, which includes clinical, MRI data samples collected over more than 20 years. included a confirmed Expanded Disability Status Scale (EDSS) score ≥3 that corresponds classifier high risk underlying pathology. analyzed within 6 months from EDSS corresponding baseline visit. Patients who further developed 6-month disability (6mCDP) were classified progressors. stratified into active/nonactive new brain/spinal cord lesions or relapses in 2 years before during follow-up. Statistical analysis log-transformed sGFAP/sNfL assessed association demographic, features associations future disability.We 257 had an average 4.0 median follow-up after 7.6 was higher (adjusted β = 1.21; 95% CI 1.04-1.42; p 0.016), first 1.17; 1.01-1.36; 0.042). not increased presence activity. Higher levels, but associated 6mCDP hazard ratio [HR] 1.71; 1.19-2.45; 0.004). The stronger low HR 2.44; 1.32-4.52; 0.005) nonactive prior sample.Higher levels correlated subsequent progression, particularly patients, whereas reflected acute Thus, may used to stratify clinical research studies trials inform care.

Language: Английский

---

Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer’s disease

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 68, P. 101335 - 101335

Published: April 1, 2021

Astrocyte reactivity is a hallmark of neuroinflammation that arises with Alzheimer's disease (AD) and nearly every other neurodegenerative condition. While astrocytes certainly contribute to classic inflammatory processes (e.g. cytokine release, waste clearance, tissue repair), newly emerging technologies for measuring targeting cell specific activities in the brain have uncovered essential roles synapse function, metabolism, neurovascular coupling, sleep/wake patterns. In this review, we use holistic approach incorporate, expand upon, neuroinflammatory concepts consider how astrocyte dysfunction/reactivity modulates multiple pathological clinical hallmarks AD. Our ever-evolving understanding signaling neurodegeneration not only revealing new drug targets treatments dementia but suggesting reimagine AD pathophysiological mechanisms.

Language: Английский

---

The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: April 12, 2024

Neuroinflammation refers to a highly complicated reaction of the central nervous system (CNS) certain stimuli such as trauma, infection, and neurodegenerative diseases. This is cellular immune response whereby glial cells are activated, inflammatory mediators liberated reactive oxygen nitrogen species synthesized. key process that helps protect brain from pathogens, but inappropriate, or protracted inflammation yields pathological states Parkinson’s disease, Alzheimer’s, Multiple Sclerosis, other disorders showcase various pathways neurodegeneration distributed in parts CNS. review reveals major neuroinflammatory signaling associated with neurodegeneration. Additionally, it explores promising therapeutic avenues, stem cell therapy, genetic intervention, nanoparticles, aiming regulate neuroinflammation potentially impede decelerate advancement these conditions. A comprehensive understanding intricate connection between diseases pivotal for development future treatment strategies can alleviate burden imposed by devastating disorders.

Language: Английский

---