This review surveys preclinical and mechanistic literature suggesting doxycycline’s antioxidant, anti-inflammatory, and ER-stress–modulating activities may protect dopaminergic neurons and thus could be repurposed for Parkinson’s disease.

Repurposing an FDA-approved drug with demonstrated neuroprotective effects offers a comparatively fast translational path for PD therapeutics targeting inflammation, oxidative and ER stress, but concrete molecular mechanisms and clinical efficacy data are still limited.

Parkinson's disease (PD) is the second most common neurodegenerative disease subsequent to Alzheimers disease (AD). PD is characterized by progressive neurodegeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Notably, the management of PD is chiefly symptomatic without modifying the underlying PD neuropathology. Moreover, prolonged use of anti-PD medications may be correlated with severe harmful effects such as dyskinesia and neuronal oxidative stress. Consequently, repurposing FDA-permitted therapies with antioxidants and anti-inflammatory capacities may prevent the progression of PD neuropathology. The antibiotic doxycycline has been shown to alleviate PD neuropathology by restraining the development of neurodegeneration, neuroinflammation, oxidative stress, and endoplasmic reticulum (ER) stress. However, the molecular mechanism of doxycycline in PD is not fully explained. Hence, this review purposes to examine the various effects of doxycycline regarding its potential molecular mechanism alongside the progression of PD.