Pajoohesh-Ganji et al., Inhibition of amyloid precursor protein secretases reduces recovery after spinal cord injury. Brain Research, 2014; 1560: p. 73-82.
Say the words “amyloid precursor protein” (APP) to any student majoring in Biochemistry – and they’ll rattle off a bunch of facts for you – all centered around how, basically, APP cleavage leads to amyloid aggregation into “amyloid plaques” important for Alzheimer’s disease, but no one really knows how it works, or what purpose the protein serves when not running around ruining people’s lives. Well, no longer. Pajoohesh-Gangi et al. studied APP secretases; the enzymes that cleaves APP into Amyloid-β protein. The first reaction to this pathway would be the thought that preventing cleavage of APP would be an effective therapy for Alzheimer’s and other amyloid-implicated neurological disorders. However, it has always been postulated that Amyloid-β does actually serve a positive purpose most of the time.
Pajoohesh-Gangi et al. decided to study the effect that inhibiting amyloid secretases would have on the ability of mice to recover from spinal cord injury. The secretases were either inhibited using DAPT, an inhibitor drug, or through use of amyloid secretase knockout mice. When the recovery of mice after induced spinal cord injury was measured, both methods of inhibiting amyloid secretases were found to inhibit functional recovery, both in terms of the white matter spared as well as demonstrated through behavioral testing of the mice. Thus, although a specific method was not elucidated, a positive effect of amyloid-β protein has finally been shown in certain scenarios.
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