Perspective Chapter - NMDA Treatments for CNS Disorders

The N-methyl-D-aspartate receptor (NMDAR), a glutamate-gated ion channel, mediates various physiological functions, such as synaptic plasticity, learning, and memory. Any homeostatic dysregulation of NMDAR may cause central nervous system (CNS) disorders, such as Alzheimer’s disease, depression, and schizophrenia. The involvement of NMDA dysfunction promotes advanced research on developing NMDAR pharmaceutics for treating CNS disorders. NMDAR enhancers, by direct or indirect potentiating NMDAR functions, have been used to recover NMDAR functions for treating schizophrenia. Interestingly, NMDAR blockers, by direct or indirect inhibiting NMDAR functions, have also been utilized for CNS disorders, such as Alzheimer’s disease and depression. In this chapter, the current strategy of NMDAR modulation for CNS disorders are elaborated on to discern underlying neurophysiological mechanisms of how homeostatic regulation of NMDAR plays a vital role in the normal and pathological states, respectively.

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CX3CL1/CX3CR1 in Alzheimer’s Disease: A Target for Neuroprotection

BioMed Research International ◽

10.1155/2016/8090918 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Peiqing Chen ◽

Wenjuan Zhao ◽

Yanjie Guo ◽

Juan Xu ◽

Ming Yin

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Central Nervous System ◽

Nervous System ◽

Early Diagnosis ◽

Vital Role ◽

Therapeutic Interventions ◽

Chemokine Ligand ◽

The Central Nervous System ◽

Receptor Cx3cr1

CX3C chemokine ligand 1 (CX3CL1) is an intriguing chemokine belonging to the CX3C family. CX3CL1 is secreted by neurons and plays an important role in modulating glial activation in the central nervous system after binding to its sole receptor CX3CR1 which mainly is expressed on microglia. Emerging data highlights the beneficial potential of CX3CL1-CX3CR1 in the pathogenesis of Alzheimer’s disease (AD), a common progressive neurodegenerative disease, and in the progression of which neuroinflammation plays a vital role. Even so, the importance of CX3CL1/CX3CR1 in AD is still controversial and needs further clarification. In this review, we make an attempt to present a concise map of CX3CL1-CX3CR1 associated with AD to find biomarkers for early diagnosis or therapeutic interventions.

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Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1740265 ◽

2021 ◽

Author(s):

Tamara K. Stevenson ◽

Shannon J. Moore ◽

Geoffrey G. Murphy ◽

Daniel A. Lawrence

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Central Nervous System ◽

Nervous System ◽

Synaptic Plasticity ◽

Learning And Memory ◽

Blood Brain Barrier ◽

Brain Barrier Permeability ◽

Tissue Plasminogen ◽

The Central Nervous System

AbstractTissue plasminogen activator's (tPA) fibrinolytic function in the vasculature is well-established. This specific role for tPA in the vasculature, however, contrasts with its pleiotropic activities in the central nervous system. Numerous physiological and pathological functions have been attributed to tPA in the central nervous system, including neurite outgrowth and regeneration; synaptic and spine plasticity; neurovascular coupling; neurodegeneration; microglial activation; and blood–brain barrier permeability. In addition, multiple substrates, both plasminogen-dependent and -independent, have been proposed to be responsible for tPA's action(s) in the central nervous system. This review aims to dissect a subset of these different functions and the different molecular mechanisms attributed to tPA in the context of learning and memory. We start from the original research that identified tPA as an immediate-early gene with a putative role in synaptic plasticity to what is currently known about tPA's role in a learning and memory disorder, Alzheimer's disease. We specifically focus on studies demonstrating tPA's involvement in the clearance of amyloid-β and neurovascular coupling. In addition, given that tPA has been shown to regulate blood–brain barrier permeability, which is perturbed in Alzheimer's disease, this review also discusses tPA-mediated vascular dysfunction and possible alternative mechanisms of action for tPA in Alzheimer's disease pathology.

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