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Glial cells, including microglia and astrocytes, facilitate the survival and health of all cells
within the Central Nervous System (CNS) by secreting a range of growth factors and contributing to
tissue and synaptic remodeling. Microglia and astrocytes can also secrete cytotoxins in response to
specific stimuli, such as exogenous Pathogen-Associated Molecular Patterns (PAMPs), or endogenous
Damage-Associated Molecular Patterns (DAMPs). Excessive cytotoxic secretions can induce the death
of neurons and contribute to the progression of neurodegenerative disorders, such as Alzheimer’s disease
(AD). The transition between various activation states of glia, which include beneficial and detrimental
modes, is regulated by endogenous molecules that include DAMPs, cytokines, neurotransmitters,
and bioactive lipids, as well as a diverse group of mediators sometimes collectively referred to as
Resolution-Associated Molecular Patterns (RAMPs). RAMPs are released by damaged or dying CNS
cells into the extracellular space where they can induce signals in autocrine and paracrine fashions by
interacting with glial cell receptors. While the complete range of their effects on glia has not been described
yet, it is believed that their overall function is to inhibit adverse CNS inflammatory responses,
facilitate tissue remodeling and cellular debris removal. This article summarizes the available evidence
implicating the following RAMPs in CNS physiological processes and neurodegenerative diseases:
cardiolipin (CL), prothymosin α (ProTα), binding immunoglobulin protein (BiP), heat shock protein
(HSP) 10, HSP 27, and αB-crystallin. Studies on the molecular mechanisms engaged by RAMPs could
identify novel glial targets for development of therapeutic agents that effectively slow down neuroinflammatory
disorders including AD.
A novel dominant D109A CRYAB mutation in a family with myofibrillar myopathy affects αB-crystallin structure
