Neuroinflammation and fractalkine signaling in Alzheimer's disease.
Dylan J FinneranKevin R NashPublished in: Journal of neuroinflammation (2019)
Alzheimer's disease (AD) is a progressive, neurodegenerative disorder, and the most common form of dementia. As the understanding of AD has progressed, it is now believed that AD is an amyloid-initiated tauopathy with neuroinflammation serving as the link between amyloid deposition, tau pathology, and neurodegeneration. As microglia are the main immune effectors in the central nervous system, they have been the focus of attention in studies investigating the neuroinflammatory component of AD. Therefore, recent work has focused on immunomodulators, which can alter microglial activation without suppressing activity, as potential therapeutics for AD. Fractalkine (CX3CL1; FKN), a unique chemokine with a one-to-one relationship with its receptor, signals through its cognate receptor (CX3CR1) to reduce expression of pro-inflammatory genes in activated microglia. Disrupting FKN signaling has opposing effects on the two hallmark pathologies of AD, but over-expressing a soluble FKN has been shown to reduce tau pathology while not altering amyloid pathology. Recently, differential signaling has been reported when comparing two cleavage variants of soluble FKN. These differential effects may explain recent studies reporting seemingly conflicting results regarding the effect of FKN over expression on AD pathologies.
Keyphrases
- inflammatory response
- poor prognosis
- lipopolysaccharide induced
- cerebrospinal fluid
- traumatic brain injury
- lps induced
- neuropathic pain
- multiple sclerosis
- cognitive decline
- emergency department
- working memory
- small molecule
- mild cognitive impairment
- genome wide
- gene expression
- copy number
- spinal cord injury
- long non coding rna
- spinal cord
- oxidative stress
- case control
- blood brain barrier
- dna binding
- electronic health record
- wild type
- type iii