Curli protein: A potential contributor to α-synucleopathy in Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by the gradual loss of dopaminergic neurons in the substantia nigra, resulting in both motor and non-motor symptoms. A defining feature of PD pathology is the presence of Lewy bodies, which are intracellular inclusions primarily composed of aggregated alpha-synuclein (α-syn) proteins. The abnormal buildup of α-syn, referred to as α-synucleopathy, is a key aspect of PD and other neurodegenerative conditions. Recent research indicates that bacterial amyloids, such as curli proteins produced by Escherichia coli, may influence α-syn aggregation, potentially playing a role in PD development. These discoveries provide a new perspective on the involvement of microbial factors in neurodegenerative diseases, suggesting that curli proteins can cross-seed with α-syn and enhance its aggregation. Understanding these interactions opens up new therapeutic possibilities, including methods to inhibit curli production, prevent curli-α-syn interactions, or target the resulting pathological aggregates. Such therapeutic strategies could offer promising new ways to slow or stop the progression of PD and improve outcomes for patients.