Alzheimer.27s disease Apomorphine

flow chart depicting states leading alzheimer s disease. apomorphine shown in role, proposed himeno et al., hindering progression of disease.

when proteins in cell undergo misfolding due damage, misprocessing, or mutation can lead alteration of protein’s secondary structure , change amino acid residues accessible. in many cases of protein aggregation, hydrophobic residues, on interior of soluble proteins, become arranged on solvent exposed surface. can lead interactions between hydrophobic regions of multiple proteins, entropically favorable reduce surface area of hydrophobicity exposed. formation of few molecules form oligomer still soluble, grows , continues aggregate product fall out of solution, causing damage cell manifesting in proteopathic diseases. recent studies have shown pre-fibril aggregates toxic through hydrophobic interactions various cellular components causing cytoskeletal rearrangements , loss of cell-to-cell contacts.

apomorphine reported inhibitor of amyloid beta protein (aβ) fiber formation , potential therapeutic alzheimer s disease (ad) under amyloid hypothesis. apomorphine , small molecule relatives found promote oligomerization of aβ40 group of molecules, inhibit more advanced fibril formation occurring. mechanism of protection offered small molecules thought due autoxidation occurs @ hydroxyl groups. once functional group altered, inhibitory effect seen decrease, reducing either indirect or direct interference of fibril formation.

the protective effects of apomorphine tested in mouse models mutations in genes related ad, such amyloid precursor protein (app) gene, implicated in amyloid molecule build-up. apomorphine seen improve memory function through increased successful completion of morris water maze. levels of aberrant proteins lead neuronal disruption tested in brains of mice. treatment seen decrease intraneuronal levels of more aggressive aβ42 molecule when compared control mice. result consistent finding protein linked ad, tau protein, seen decrease apomorphine treatment. apomorphine shown promote aβ degradation , inhibit formation through anti-oxidative properties. moderate doses shown provide improvements while overuse provided no benefits , may cause toxicity.