Preclinical assessment of a ganglioside-targeted therapy for Parkinson’s disease with the first-in-class adaptive peptide AmyP53 DOI Creative Commons
Jacques Fantini, Fodil Azzaz, Anaïs Aulas

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 17, 2025

We propose a new concept for the treatment of Parkinson's disease (PD), which considers that its root cause, α-synuclein, is an intrinsically disordered protein (IDP) difficult to target by classic approaches. Upon binding lipid raft gangliosides, α-synuclein shifts from random coil α-helix, forming Ca2+-permeable oligomeric pores triggering neurotoxicity cascade. used α-synuclein-ganglioside interaction as guideline design therapeutic peptide (AmyP53) combines respective flexible ganglioside-binding domains and Alzheimer's β-amyloid protein. AmyP53 adaptive peptide, first representant class. It acts competitive inhibitor oligomer formation in brain cell membranes prevents subsequent downstream synaptotoxicity, including loss dopaminergic neurons animal injection model PD. active against both wild-type mutant forms α-synuclein. administered intranasally without side effects. This "target (gangliosides), not arrow (IDP)" distinct centric approaches did cure PD so far.

Язык: Английский

Expanding the horizons of bicyclol in multiple diseases: Mechanisms, therapeutic implications and challenges DOI

Heng Liu,

Ziyi Yang, Jia Li

и другие.

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177381 - 177381

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Preclinical assessment of a ganglioside-targeted therapy for Parkinson’s disease with the first-in-class adaptive peptide AmyP53 DOI Creative Commons
Jacques Fantini, Fodil Azzaz, Anaïs Aulas

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 17, 2025

We propose a new concept for the treatment of Parkinson's disease (PD), which considers that its root cause, α-synuclein, is an intrinsically disordered protein (IDP) difficult to target by classic approaches. Upon binding lipid raft gangliosides, α-synuclein shifts from random coil α-helix, forming Ca2+-permeable oligomeric pores triggering neurotoxicity cascade. used α-synuclein-ganglioside interaction as guideline design therapeutic peptide (AmyP53) combines respective flexible ganglioside-binding domains and Alzheimer's β-amyloid protein. AmyP53 adaptive peptide, first representant class. It acts competitive inhibitor oligomer formation in brain cell membranes prevents subsequent downstream synaptotoxicity, including loss dopaminergic neurons animal injection model PD. active against both wild-type mutant forms α-synuclein. administered intranasally without side effects. This "target (gangliosides), not arrow (IDP)" distinct centric approaches did cure PD so far.

Язык: Английский

Процитировано

0