Author(s):  
Henrik Zetterberg ◽  
Jonathan M. Schott

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.


2016 ◽  
Vol 12 ◽  
pp. P1085-P1085
Author(s):  
Valeria Calsolaro ◽  
Azhaar Ashraf ◽  
Zhen Fan ◽  
David J. Brooks ◽  
Paul Edison

2014 ◽  
Vol 07 (03) ◽  
pp. 1350049 ◽  
Author(s):  
Sheng Song ◽  
Wei Chen ◽  
Feifan Zhou

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.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1449
Author(s):  
Jae-Won Lee ◽  
Wanjoo Chun ◽  
Hee Jae Lee ◽  
Seong-Man Kim ◽  
Jae-Hong Min ◽  
...  

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.


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