Inhibition of colony stimulating factor-1 receptor (CSF-1R) as a potential therapeutic strategy for neurodegenerative diseases: opportunities and challenges DOI Creative Commons
Jinming Han, Violeta Chiţu, E. Richard Stanley

et al.

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(4)

Published: April 1, 2022

Abstract Microglia are specialized dynamic immune cells in the central nervous system (CNS) that plays a crucial role brain homeostasis and disease states. Persistent neuroinflammation is considered hallmark of many neurodegenerative diseases, including Alzheimer’s (AD), Parkinson's (PD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS) primary progressive multiple (MS). Colony stimulating factor 1-receptor (CSF-1R) predominantly expressed on microglia its expression significantly increased diseases. Cumulative findings have indicated CSF-1R inhibitors can beneficial effects preclinical models. Research using has now been extended into non-human primates humans. This review article summarizes most recent advances different conditions AD, PD, HD, ALS MS. Potential challenges for translating these clinical practice presented.

Language: Английский

Role of neuroinflammation in neurodegeneration development DOI Creative Commons
Weifeng Zhang, Dan Xiao, Qinwen Mao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 12, 2023

Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.

Language: Английский

Citations

577
The semantics of microglia activation: neuroinflammation, homeostasis, and stress DOI Creative Commons
Samuel C. Woodburn, Justin L. Bollinger, Eric S. Wohleb

et al.

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: Nov. 6, 2021

Microglia are emerging as critical regulators of neuronal function and behavior in nearly every area neuroscience. Initial reports focused on classical immune functions microglia pathological contexts, however, immunological concepts from these studies have been applied to describe neuro-immune interactions the absence disease, injury, or infection. Indeed, terms such 'microglia activation' 'neuroinflammation' used ubiquitously changes disparate contexts; particularly stress research, where prompt undue comparisons conditions. This creates a barrier for investigators new neuro-immunology ultimately hinders our understanding effects microglia. As more seek understand role neurobiology behavior, it is increasingly important develop standard methods study define microglial phenotype function. In this review, we summarize primary research physiological contexts. Further, propose framework better microglia1 chronic stress. approach will enable precise characterization different which should facilitate development microglia-directed therapeutics psychiatric neurological disease.

Language: Английский

Citations

456
Microglia: Immune and non-immune functions DOI
Katharina Borst, Anaëlle Dumas, Marco Prinz

et al.

Immunity, Journal Year: 2021, Volume and Issue: 54(10), P. 2194 - 2208

Published: Oct. 1, 2021

Language: Английский

Citations

454
Microglia regulation of synaptic plasticity and learning and memory DOI Creative Commons
Miou Zhou,

Jessica Cornell,

Shelbi Salinas

et al.

Neural Regeneration Research, Journal Year: 2021, Volume and Issue: 17(4), P. 705 - 705

Published: Aug. 29, 2021

Microglia are the resident macrophages of central nervous system. possess varied morphologies and functions. Under normal physiological conditions, microglia mainly exist in a resting state constantly monitor their microenvironment survey neuronal synaptic activity. Through C1q, C3 CR3 "Eat Me" CD47 SIRPα "Don't Eat complement pathways, as well other pathways such CX3CR1 signaling, regulate pruning, process crucial for promotion synapse formation regulation activity plasticity. By mediating play an important role experience-dependent plasticity barrel cortex visual after whisker removal or monocular deprivation, also learning memory, including modulation memory strength, forgetfulness, quality. As response to brain injury, infection neuroinflammation, become activated increase number. Activated change amoeboid shape, migrate sites inflammation secrete proteins cytokines, chemokines reactive oxygen species. These molecules released by can lead deficits associated with aging, Alzheimer's disease, traumatic HIV-associated neurocognitive disorder, neurological mental disorders autism, depression post-traumatic stress disorder. With focus on recently published literature, here we reviewed studies investigating how modulate disease-related deficits. summarizing function these processes, aim provide overview discuss possibility manipulation therapeutic ameliorate cognitive disorders.

Language: Английский

Citations

307
The neurobiology of long COVID DOI Creative Commons
Michelle Monje, Akiko Iwasaki

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3484 - 3496

Published: Oct. 7, 2022

Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 represent major component the post-acute syndrome, also known as long COVID. Here, we review what is understood about pathobiology impact on CNS discuss possible neurobiological underpinnings cognitive affecting survivors. We propose chief mechanisms that may contribute to this emerging health crisis.

Language: Английский

Citations

299
Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS DOI
Travis E. Faust, Georgia Gunner, Dorothy P. Schafer

et al.

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(11), P. 657 - 673

Published: Sept. 20, 2021

Language: Английский

Citations

266
Synaptic basis of Alzheimer’s disease: Focus on synaptic amyloid beta, P-tau and mitochondria DOI
Albin John, P. Hemachandra Reddy

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 65, P. 101208 - 101208

Published: Nov. 4, 2020

Language: Английский

Citations

264
Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines DOI Creative Commons
Peng Cao,

Changmao Chen,

An Liu

et al.

Neuron, Journal Year: 2021, Volume and Issue: 109(16), P. 2573 - 2589.e9

Published: July 6, 2021

Language: Английский

Citations

240
GABA-receptive microglia selectively sculpt developing inhibitory circuits DOI Creative Commons
Emilia Favuzzi, Shuhan Huang, Giuseppe-Antonio Saldi

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(15), P. 4048 - 4063.e32

Published: July 1, 2021

Language: Английский

Citations

217
Neuronal hyperexcitability in Alzheimer’s disease: what are the drivers behind this aberrant phenotype? DOI Creative Commons
Helena Targa Dias Anastacio, Natalie Matosin, Lezanne Ooi

et al.

Translational Psychiatry, Journal Year: 2022, Volume and Issue: 12(1)

Published: June 22, 2022

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to loss of cognitive abilities and ultimately, death. With no cure available, limited treatments mostly focus on symptom management. Identifying early changes in the course may provide new therapeutic targets halt or reverse progression. Clinical studies have shown that cortical hippocampal hyperactivity are feature shared by patients stages disease, progressing hypoactivity during later neurodegeneration. The exact mechanisms causing neuronal excitability not fully characterized; however, animal cell models provided insights into some factors involved this phenotype. In review, we summarize evidence for over AD onset progression molecular underpinning these differences. Specifically, discuss contributors aberrant excitability, including abnormal levels intracellular Ca 2+ glutamate, pathological amyloid β (Aβ) tau, genetic risk factors, APOE , impaired inhibitory interneuron glial function. light recent research indicating hyperexcitability could be predictive marker dysfunction, further argue phenotype leveraged improve diagnosis treatment AD, present potential future development.

Language: Английский

Citations

197