NISOD-LIKE COMPOUND AND ITS DERIVATIVES FOR THE PREVENTION AND TREATMENT OF NEURODEGENERATIVE DISORDERS

摘要

The accumulation of abnormal proteins in neurodegenerative disorders is considered to induce oxidative stress and lead to cell death. Thus suppression of abnormal protein aggregation and reducing oxidative stress or reactive oxygen species (ROS) are expected to inhibit a wide range of harmful downstream events, providing an observation for identifying the potential prevention and treatment of neurodegenerative disorders comprising spinocerebellar ataxia (SCA), Alzheimer's disease (AD) or Parkinson's disease (PD). In the present invention, there are several cell and animal experiment models for SCA, AD and PD established, and NiSOD-like compounds were applied to these experiment models. The results have demonstrated how NiSOD-like compounds are likely to work in suppressing abnormal protein aggregation and reducing oxidative stress; in addition, the results were also confirmed with brain slice culture of SCA17 transgenic mice and AD mice, brain tissues immunostaining of PD mice, and SCA17 transgenic, AD and PD mice.

主权项

1. A nickel superoxide dismutase-like (NiSOD-like) compound (NiBDPP) or derivatives thereof as a pharmaceutical composition for prevention and treatment of a neurodegenerative disorder, wherein the NiSOD-like compound or derivatives thereof is a five-coordinate derivative having a structural formula (I): wherein R1 denotes H or -A-R′; wherein A denotes O or N; wherein R′ is H, an alkoxy group, an amino acid group, or a polymeric group; wherein said polymeric group is a polyethyleneoxy group, a polydimethylsiloxane group, or polyurethane; wherein R2 is H or a para-substituent of a phenyl ring, said para-substituent of said phenyl ring is selected from a group consisting of alkyl groups, alkoxy groups, silane groups, amino groups, alkyl amino groups, and an hydroxyl group; wherein R3 is a H or a para-substituent of a pyridine ring, said para-substituent of said pyridine ring is selected from a group consisting of amino groups, alkyl amino groups, siloxane amino groups, and siloxane amino groups which attach to a Fe3O4/SiO2 magnetic nanoparticle; and wherein Ni is a nickel(II) or nickel(III) ion.