Blood-Brain Barrier Penetration Test
Objective: Assessment of FPS-ZM1's ability to cross the blood-brain barrier in mice and its effects on amyloid β-mediated brain disorder
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Materials1
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Protocol Steps
Administer FPS-ZM1 to transgenic mice
FPS-ZM1 was administered to aged APP sw/0 transgenic mice overexpressing human amyloid β-precursor protein
Note: Mice had established amyloid β pathology at time of treatment
View evidence from paper
“In aged APP sw/0 mice overexpressing human Aβ-precursor protein, a transgenic mouse model of AD with established Aβ pathology, FPS-ZM1 inhibited RAGE-mediated influx”
Assess blood-brain barrier penetration
Evaluate FPS-ZM1's ability to cross the blood-brain barrier and reach brain tissue
Note: FPS-ZM1 was confirmed to readily cross the BBB
View evidence from paper
“FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB)”
Measure RAGE binding in brain
Determine that FPS-ZM1 bound exclusively to RAGE in the brain tissue
Note: Exclusive binding to RAGE was confirmed
View evidence from paper
“In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited β-secretase activity and Aβ production”
Assess amyloid β levels in brain
Measure amyloid β-40 and amyloid β-42 levels in brain tissue following FPS-ZM1 treatment
Note: Amyloid β levels were markedly reduced
View evidence from paper
“Blockade of RAGE actions at the BBB and in the brain reduced Aβ40 and Aβ42 levels in brain markedly”
Evaluate cognitive performance
Assess cognitive function in treated mice to determine if normalized performance was achieved
Note: Cognitive performance was normalized in aged APP sw/0 mice
View evidence from paper
“normalized cognitive performance and cerebral blood flow responses in aged APP sw/0 mice”
Measure cerebral blood flow responses
Evaluate cerebral blood flow responses in treated mice
Note: Cerebral blood flow responses were normalized
View evidence from paper
“normalized cognitive performance and cerebral blood flow responses in aged APP sw/0 mice”