Estrogen role in parkinson disease: unlocking new pathways and therapeutic potentials

Parkinson's disease (PD) is a common neurodegenerative condition marked by both motor and nonmotor impairments. According to recent data, estrogen may have a major impact on PD, and its neuroprotective properties may open up new avenues for treatment. Female gonadal hormones, especially estradiol, have been implicated in regulating the risk and symptoms of PD, as evidenced by epidemiological studies that have revealed sex variations in the disease's incidence and course. The biology of estrogen receptors (ERα, ERβ, and GPER) and their location in the nervous system are examined in this overview, with an emphasis on their potential for neuroprotection. This review delves into estrogen's neuroprotective effects, focusing on its interaction with estrogen receptors and its activation of critical molecular pathways. The cAMP-PKA-CREB pathway promotes neuronal survival, while the MAPK and NF-κB pathways reduce neuroinflammation. Furthermore, the PI3K-Akt pathway enhances anti-apoptotic signaling, and the IP3-DAG pathway supports calcium-mediated neuronal processes. Collectively, these mechanisms reveal how estrogen mitigates neuronal damage and influences PD pathophysiology. By elucidating the molecular mechanisms underlying estrogen's effects, this review underscores its potential as a therapeutic target for PD. Future research on estrogen receptor modulation and signaling may unlock novel interventions to address both motor and nonmotor symptoms of PD.