Prolactin in Neurodegenerative Diseases: Mechanistic Insights from Alzheimer’s and Parkinson’s Diseases

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are progressive neurodegenerative disorders in which oxidative stress, neuroinflammation, mitochondrial dysfunction, abnormal protein handling, and neuronal apoptosis interact over time. Prolactin (PRL), traditionally recognized for its reproductive functions, is also a pleiotropic neuroendocrine signal whose receptor (PRLR) is expressed in neurons, astrocytes, and other cells of the nervous system. This narrative review examines whether PRL-related signaling could influence biological processes relevant to AD and PD and evaluates the limitations of circulating PRL as a clinical marker. Experimental studies support receptor-dependent protective effects under defined oxidative and excitotoxic conditions. In hippocampal neurons, PRL reduced reactive oxygen species, lipid peroxidation, and apoptosis through mechanisms involving NF-κB and suppression of BAX and NOX۴, whereas in astrocytes it activated a STAT۳/NRF۲-associated antioxidant response. Age-related changes in hippocampal PRLR isoform expression may further modify neural responsiveness to PRL during ageing. In PD, however, circulating and cerebrospinal-fluid PRL are strongly influenced by dopamine replacement and levodopa exposure, limiting interpretation of PRL concentrations as direct indicators of neurodegenerative activity. Human evidence also remains inconclusive; a systematic review and meta-analysis found no significant overall difference in serum PRL between individuals with neurodegenerative diseases and controls. Overall, current evidence supports PRL as a context-dependent neuroendocrine modulator rather than a universally neuroprotective or pathogenic factor. Future studies should integrate PRLR isoform profiling, cell- and region-specific measurements, longitudinal clinical phenotyping, and medication-aware analyses.

کلیدواژه ها:

Prolactin ، Alzheimer’s disease ، Parkinson’s disease ، neuroinflammation ، neuroprotection