Targeting Platelet Activating Factor Signaling for Therapeutic Benefits in Neurodegenerative Disorders

Neurodegenerative disorders (NDs), including dementia, Alzheimer's disease (AD), and Parkinson's disease (PD), are age-related diseases closely associated with chronic inflammation, oxidative stress, gene mutations, autoimmune-derived inflammation, and other external risk factors. They are characterized by progressive neuronal loss, cognitive decline, and/or motor dysfunction, with chronic inflammation being a key player in intensifying NDs' occurrence. One of the most important molecular inflammatory mediators linking inflammation to NDs is the platelet-activating factor (PAF) and its pivotal signaling for regulating neuroinflammation, apoptosis, and neuronal damage. Dysregulation of PAF activity and metabolism/levels, along with overexpression of its receptor (PAF-R) have been associated with exacerbated inflammatory responses, further aggravating neurodegeneration. This article highlights the role of PAF in neurodegeneration, with a particular focus on novel insights into the potential medicinal use of PAF inhibitors for the prevention and treatment of neurodegenerative diseases. We evaluate the recently proposed concept of targeting the PAF signaling pathway through either natural and/or synthetic inhibitors or a combination of both. It explores the potential of these inhibitors to offer significant preventative and therapeutic benefits against NDs, likely through anti-inflammatory anti-aging effects and by slowing down the disease progression and preserving cognitive and motor dysfunction. Current status and future perspectives of such therapeutic approaches are also discussed.