A moderate metal-binding hydrazone meets the criteria for a bioinorganic approach towards Parkinson's disease: Therapeutic potential, blood-brain barrier crossing evaluation and preliminary toxicological studies

CUKIERMAN DS, PINHEIRO AB, CASTIÑEIRAS-FILHO SL, DA SILVA AS, MIOTTO MC, DE FALCO A, DE P RIBEIRO T, MAISONETTE S, DA CUNHA AL, HAUSER-DAVIS RA, LANDEIRA-FERNANDEZ J, AUCÉLIO RQ, OUTEIRO TF, PEREIRA MD, FERNÁNDEZ CO, REY NA.

JOURNAL OF INORGANIC BIOCHEMISTRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2017

0162-0134

Alzheimer's and Parkinson's diseases share similar amyloidogenic mechanisms, in which metal ions might playan important role. In this last neuropathy,misfolding and aggregation of α-synuclein (α-Syn) are crucial pathologicalevents. A moderate metal-binding compound, namely, 8-hydroxyquinoline-2-carboxaldehydeisonicotinoyl hydrazone (INHHQ),whichwas previously reported as a potential ?Metal-Protein Attenuating Compound?for Alzheimer's treatment, is well-tolerated by healthy Wistar rats and does not alter their major organweights, as well as the tissues' reduced glutathione and biometal levels, at a concentration of 200 mg kg−1.INHHQ definitively crosses the blood-brain barrier and can be detected in the brain of rats so late as 24 h afterintraperitoneal administration. After 48 h, brain clearance is complete. INHHQ is able to disrupt, in vitro, anomalouscopper-α-Syn interactions, through a mechanism probably involving metal ions sequestering. This compoundis non-toxic to H4 (human neuroglioma) cells and partially inhibits intracellular α-Syn oligomerization.INHHQ, thus, shows definite potential as a therapeutic agent against Parkinson's as well.© 2017 Elsevier Inc