Abstract
Alzheimer’s disease is the most common neurodegenerative disorder characterized by the presence of β-amyloid aggregates deposited as senile plaques and by the presence of neurofibrillary tangles of tau protein. To date, there is a broad consensus on the idea that neuroinflammation is one of the most important component in Alzheimer’s disease pathogenesis. Chemokines and their receptors, beside the well-known role in the immune system, are widely expressed in the nervous system, where they play a significant role in the neuroinflammatory processes. Prokineticins are a new family of chemokine-like molecules involved in numerous physiological and pathological processes including immunity, pain, inflammation, and neuroinflammation. Prokineticin 2 (PROK2) and its receptors PKR1 and PKR2 are widely expressed in the central nervous system in both neuronal and glial cells. In Alzheimer’s disease, PROK2 sustains the neuroinflammatory condition and contributes to neurotoxicity, since its expression is strongly upregulated by amyloid-β peptide and reversed by the PKR antagonist PC1. This review aims to summarize the current knowledge on the neurotoxic and/or neuroprotective function of chemokines in Alzheimer’s disease, focusing on the prokineticin system: it represents a new field of investigation that can stimulate the research of innovative pharmacotherapeutic strategies.
Highlights
Alzheimer’s disease is the most common neurodegenerative disorder characterized by the presence of β-amyloid aggregates deposited as senile plaques and by the presence of neurofibrillary tangles of tau protein
Prokineticin 2 (PROK2) and its receptors prokineticin receptor 1 (PKR1) and PKR2 are widely expressed in the central nervous system in both neuronal and glial cells
This review aims to summarize the current knowledge on the neurotoxic and/ or neuroprotective function of chemokines in Alzheimer’s disease, focusing on the prokineticin system: it represents a new field of investigation that can stimulate the research of innovative pharmacotherapeutic strategies
Summary
Alzheimer’s disease is the most common neurodegenerative disorder characterized by the presence of β-amyloid aggregates deposited as senile plaques and by the presence of neurofibrillary tangles of tau protein. The histopathological hallmarks of AD are extracellular senile plaques that are aggregates of amyloid-β (Aβ) peptide, and intracellular aggregation of hyperphosphorylated tau protein that forms neurofibrillary tangles (Haass and Selkoe, 2007; Huang and Mucke, 2012) This aggregation causes a neurotoxic cascade, which, in turn, leads to neuronal degeneration and atrophy of the brain regions involved in memory and cognitive impairment (temporal and parietal lobe, pre-frontal cortex, and hippocampus), increasing, in this way, brain neuroinflammation (Raskin et al, 2015; Bronzuoli et al, 2016). Most of the chemokines and their receptors contribute to the neuroinflammatory component of AD by recruiting peripheral blood monocytes and promoting glial cell activation, even if emerging data hypothesize for some of them, a neuroprotective role
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