S3-02-04: MICROGLIAL ACTIVATION IN NEURODEGENERATIVE DISEASES: OPPORTUNITIES FOR THERAPEUTIC INTERVENTION

2006 ◽  
Vol 14 (7S_Part_18) ◽  
pp. P995-P995
Author(s):  
Diego Gomez-Nicola
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Intervention ◽  
Microglial Activation

scholarly journals The Ambiguous Role of Microglia in Aβ Toxicity: Chances for Therapeutic Intervention

2020 ◽  
Vol 18 (5) ◽  
pp. 446-455 ◽  
Author(s):  
Sara Merlo ◽  
Simona Federica Spampinato ◽  
Grazia Ilaria Caruso ◽  
Maria Angela Sortino
Keyword(s):  
Disease Progression ◽  
Therapeutic Intervention ◽  
Microglial Activation ◽  
Wide Spectrum ◽  
Direct Interaction ◽  
Pharmacological Intervention ◽  
High Complexity ◽  
Regenerative Processes ◽  
Multiple Receptors

Amyloid-β (Aβ) has long been shown to be critical in Alzheimer’s disease pathophysiology. Microglia contributes to the earliest responses to Aβ buildup, by direct interaction through multiple receptors. Microglial cells operate Aβ clearance and trigger inflammatory/regenerative processes that take place in the long years of silent disease progression that precede symptomatic appearance. But in time and with aging, the fine balance between pro- and anti-inflammatory activity of microglia deranges, negatively impacting its Aβ-clearing ability. Furthermore, in recent years, microglial activation has proven to be much more complex than the mere dichotomic pro/antiinflammatory polarization previously accepted. Microglia can display a wide spectrum of phenotypes, which can even be mixed. On these bases, it is evident that while pharmacological intervention aiding microglia to prolong its ability to cope with Aβ buildup could be extremely relevant, its feasibility is hampered by such high complexity, which still needs to be completely understood.

Fluid Biomarkers Indicative of Neurodegenerative Diseases

2016 ◽  
Author(s):  
Henrik Zetterberg ◽  
Jonathan M. Schott
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Microglial Activation ◽  
Psychiatric Symptoms ◽  
Neuronal Loss ◽  
Protein Accumulation ◽  
Time Line ◽  
The Past ◽  
Neurodegenerative Process ◽  
Disease Specific

A major unifying feature of neurodegenerative diseases (NDDs) is excessive neuronal loss. Depending on when and where this occurs, patients may express distinct neurological and psychiatric symptoms. Neurodegeneration is accompanied by protein aggregation, inflammation, and microglial activation that may be drivers of the disease or in some circumstances may be protective reactions to the neurodegenerative process. A key development over the past decade has been our ability to leverage these accompanying central nervous system changes to develop clinically impactful biomarkers of specific NDDs. This has been crucial in helping us develop an understanding the time line of progression of these diseases, in their early diagnosis and to help target patients appropriately in therapeutic clinical trials, This chapter gives an overview of both established and novel fluid biomarkers for neurodegeneration, protein accumulation, inflammation, and microglial activation across different neurodegenerative diseases. Common as well as disease-specific biomarker changes in cerebrospinal fluid and blood are emphasized.

scholarly journals Effects of LPLI on microglial phagocytosis in LPS-induced neuroinflammation model

2014 ◽  
Vol 07 (03) ◽  
pp. 1350049 ◽  
Author(s):  
Sheng Song ◽  
Wei Chen ◽  
Feifan Zhou
Keyword(s):  
Neurodegenerative Diseases ◽  
Microglial Activation ◽  
Actin Polymerization ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Dominant Negative ◽  
Microglial Phagocytosis ◽  
Dominant Negative Form ◽  
Phagocytic Response ◽  
Negative Form

Microglial activation plays an important role in neurodegenerative diseases. Once activated, they have macrophage-like capabilities, which can be beneficial by phagocytosis and harmful by secretion of neurotoxins. However, the resident microglia always fail to trigger an effective phagocytic response to clear dead cells or Aβ deposits during the progression of neurodegeneration. Therefore, the regulation of microglial phagocytosis is considered a useful strategy in searching for neuroprotective treatments. In this study, our results showed that low-power laser irradiation (LPLI) (20 J/cm2) could enhance microglial phagocytic function in LPS-activated microglia. We found that LPLI-mediated microglial phagocytosis is a Rac-1-dependent actin-based process, that a constitutively activated form of Rac1 (Rac1Q61L) induced a higher level of actin polymerization than cells transfected with wild-type Rac1, whereas a dominant negative form of Rac1 (Rac1T17N) markedly suppressed actin polymerization. In addition, the involvement of Rac1 activation after LPLI treatment was also observed by using a Raichu fluorescence resonance energy transfer (FRET)-based biosensor. We also found that PI3K/Akt pathway was required in the LPLI-induced Rac1 activation. Our research may provide a feasible therapeutic approach to control the progression of neurodegenerative diseases.

scholarly journals The Role of Microglia in the Development of Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1449
Author(s):  
Jae-Won Lee ◽  
Wanjoo Chun ◽  
Hee Jae Lee ◽  
Seong-Man Kim ◽  
Jae-Hong Min ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Neurodegenerative Diseases ◽  
Microglial Activation ◽  
Therapeutic Strategy ◽  
Experimental Animal Models ◽  
Effective Therapeutic Strategy ◽  
The Central Nervous System ◽  
Animal Models Of Epilepsy ◽  
Models Of Epilepsy

Microglia play an important role in the maintenance and neuroprotection of the central nervous system (CNS) by removing pathogens, damaged neurons, and plaques. Recent observations emphasize that the promotion and development of neurodegenerative diseases (NDs) are closely related to microglial activation. In this review, we summarize the contribution of microglial activation and its associated mechanisms in NDs, such as epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), based on recent observations. This review also briefly introduces experimental animal models of epilepsy, AD, PD, and HD. Thus, this review provides a better understanding of microglial functions in the development of NDs, suggesting that microglial targeting could be an effective therapeutic strategy for these diseases.

scholarly journals Neuroinflammation in Prion Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 2196
Author(s):  
Bei Li ◽  
Meiling Chen ◽  
Caihong Zhu
Keyword(s):  
Prion Disease ◽  
Therapeutic Intervention ◽  
Neurodegenerative Disorders ◽  
Microglial Activation ◽  
Prion Diseases ◽  
Reactive Astrocytes ◽  
Novel Approach ◽  
Dual Functions

Neuroinflammation, typically manifest as microglial activation and astrogliosis accompanied by transcriptomic alterations, represents a common hallmark of various neurodegenerative conditions including prion diseases. Microglia play an overall neuroprotective role in prion disease, whereas reactive astrocytes with aberrant phenotypes propagate prions and contribute to prion-induced neurodegeneration. The existence of heterogeneous subpopulations and dual functions of microglia and astrocytes in prion disease make them potential targets for therapeutic intervention. A variety of neuroinflammation-related molecules are involved in prion pathogenesis. Therapeutics targeting neuroinflammation represents a novel approach to combat prion disease. Deciphering neuroinflammation in prion disease will deepen our understanding of pathogenesis of other neurodegenerative disorders.

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