Biofilm-Associated Amyloid Proteins Linked with the Progression of Neurodegenerative Diseases.

Biofilm-associated amyloid proteins have emerged as significant contributors to the progression of neurodegenerative diseases, representing a complex intersection of microorganisms and human health. The cross-beta sheet structure characteristic of amyloids produced by gut-colonizing bacteria remains intact, crucial for the resilience of biofilms. These amyloids exacerbate neurodegenerative disorders such as Alzheimer's and Parkinson's by cross-seeding human amyloidogenic proteins like amyloid-beta and α-synuclein, accelerating their misfolding and aggregation. Despite molecular chaperones and heat shock proteins maintaining protein homeostasis, bacterial amyloids can overwhelm them, worsening neuronal damage. Genetic variations in chaperone genes further influence amyloidogenesis and neurodegeneration. Persistent bacterial infections and inflammation compromise the blood-brain barrier, allowing inflammatory molecules and amyloids to enter the brain, perpetuating the cycle of neurodegeneration. The gut-brain axis underscores the impact of dysbiosis and gut microbiota on brain function, potentially contributing to neurodegeneration. The enhancement of biofilm resilience and antibiotic resistance by functional amyloid fibrils complicates the treatment landscape. The interplay among chaperone systems, microbial amyloids, and neurodegenerative diseases underscores the urgent need for advanced treatment strategies targeting these pathways to attenuate disease progression. Understanding the processes that relate biofilm-associated amyloids to the onset of neurological disorders is critical for diagnosing and developing novel treatment strategies.