Prodigiosin in Neurodegeneration: A Critical Review, Comparative Analysis and Translational Gap Assessment

Neurodegenerative diseases, including alzheimer’s disease (AD), parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), share interconnected pathogenic mechanisms-oxidative stress, mitochondrial dysfunction, neuroinflammation and progressive neuronal loss-for which available interventions remain largely symptomatic, sustaining interest in pleiotropic natural compounds. This critical narrative review evaluates prodigiosin-a bacterial tripyrrole pigment produced by serratia marcescens-as a candidate neuroprotective compound, situates its evidence against established natural antioxidants (Curcumin, quercetin and resveratrol) and identifies translational gaps through a structured gap analysis. A structured narrative search was conducted across PubMed, Scopus, Web of Science and Google Scholar (2010-2025), combining prodigiosin with neurodegeneration-related descriptors. Given the sparse and heterogeneous evidence base, a critical narrative rather than systematic review framework was applied. Prodigiosin may modulate multiple neuroprotective pathways: (1) Nrf2/HO-1 antioxidant activation (enhanced SOD, CAT, GPx; reduced MDA and nitric oxide); (2) NF-κB suppression (downregulated IL-1β, TNF-α, COX-2, iNOS); (3) apoptosis attenuation via Bcl-2/Bax modulation and caspase-3 reduction and (4) partial restoration of neurotransmitter and neurotrophic (BDNF) indices. However, the evidence derives predominantly from a single research cluster using aluminum chloride models and lacks pharmacokinetic characterization, blood-brain barrier penetration data, independent replication and transgenic model validation.