Enhancing Lysosomal Function in the Brain with PADK

From the SENS Foundation, a look at what might be done to remove damaging cellular aggregates, such as the amyloid beta (Aβ) implicated in Alzheimer's disease (AD), by manipulating the function of lysosomes, the cellular recycling machinery: "Dr. Ben Bahr and his colleagues with the Neurosciences Program and Division of Pharmaceutical Sciences at the University of Connecticut have for some time now been investigating the effects of elevating lysosomal activity using the lysosomal modulator Z-Phe-Ala-diazomethylketone (PADK). ... In a new study, Dr. Bahr's group has extended this work into a transgenic mouse model of AD, testing PADK's ability to retard, and to reverse, AD neuropathology and cognitive dysfunction in two models of transgenic AD mice ... . Systemic PADK injection of PADK in both models caused 3- to 8-fold increases in cathepsin B levels and similar elevations in the enzyme's activity in lysosomal cell fractions ... Accordingly PADK-induced lysosomal modulations cleared a significant amount of the intra- and extraneuronal burden of Aβ from treated mice, reducing intraneuronal Aβ regions of the hippocampus and piriform cortex by 63 - 73% in younger mice and by ~50% in older ones ... As expected, model AD mice also exhibited substantial impairment of performance on cognitive-behavioral tests including the suspended rod, exploratory habituation, and spontaneous alternation behavior in a T-maze tests. PADK-induced Aβ clearance resulted in the complete restoration of normal function in both young and old animals. ... As a tribute to the power of the cellular waste-disposal machinery, these results are impressive. Equally, they are not a solution to human brain aging. These animals, like most transgenic models of AD, exhibit no tau pathology nor significant neuronal loss - problems that will also have to be addressed in order to achieve the full prevention of AD and rejuvenation of aging brains."

Link: http://www.sens.org/research/research-blog/overtime-pay-municipal-waste-team

Comments

Will there be a clinical study with humans in the near future?

Posted by: Bill Krause at August 16th, 2011 1:24 PM

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