Neurodegenerative diseases, including alzheimer&rsquo;s disease (AD), parkinson&rsquo;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-&kappa;B suppression (downregulated IL-1&beta;, TNF-&alpha;, 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.

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

Background: Diabetes mellitus is an endocrine disorder associated with functional and structural alterations in multiple organs. Experimental diabetes can be induced in animals using streptozotocin (STZ), which selectively damages pancreatic &beta;-cells and may subsequently lead to cognitive impairment. Lipopolysaccharide (LPS)-induced neuroinflammation is a widely used model for mimicking Alzheimer&rsquo;s disease (AD)-like pathology. Comparative evaluation of these models may help clarify the relationship between metabolic dysfunction and neurodegeneration. To compare the behavioral and histopathological changes produced by STZ-induced diabetes and LPS-induced Alzheimer&rsquo;s disease animal model, with special emphasis on cognition, brain, liver and pancreas alterations. 
 
Methods: Twenty-four adult male wistar rats (10-12 weeks old; 185&plusmn;15 g) were randomly divided into three groups (n = 8 each): Group I served as control, Group II received a single intraperitoneal dose of STZ (65 mg/kg body weight) to induce diabetes and Group III received LPS (10 mg/kg body weight, i.p.) to induce AD-like pathology. Blood glucose, body temperature and body weight were recorded. Behavioral assessments were carried out using spontaneous alternation and recognition memory tests. Brain, liver and pancreas tissues were collected for histopathological examination. 
 
Result: Both STZ and LPS treatment produced significant alterations in physiological and behavioral parameters, including changes in blood glucose level, body temperature, body weight and cognitive performance. Histological examination of the brain revealed neuronal loss in the hippocampal region and aggregation of senile plaque-like deposits. Liver tissue showed central vein damage, sinusoidal alterations and glycogen accumulation. Pancreatic tissue demonstrated loss of &beta;-cells and swollen acinar cells. 
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Prodigiosin in Neurodegeneration: A Critical Review, Comparative Analysis and Translational Gap Assessment

Effect of Streptozotocin and Lipopolysaccharides on the Histopathological Changes of Brain, Liver and Pancreatic Islets of Rats