Palmitoyl protein thioesterase 1 (Ppt1)-deficient mouse neurons show alterations in cholesterol metabolism and calcium homeostasis prior to synaptic dysfunction

Altered glutamate receptor function in the cerebellum of the Ppt1−/− mouse, a murine model of infantile neuronal ceroid lipofuscinosis

“…As with many NCL variants, there is evidence suggesting a disruption of glutamatergic function in INCL (Ahtiainen et al 2007; Sitter et al 2004; Suopanki et al 2002). The Ppt1 −/− mouse model has motor coordination defects as measured by latency to fall from a rotarod (Griffey et al 2006; Macauley et al 2009).…”

Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function

“…Transcript profiling of Ppt1 −/− mouse brains indicated upregulation of genes involved in cholesterol metabolism, neuronal maturation, and calcium homeostasis, i.e. significant increases in α-synuclein [68]. These alterations are supported by a gene modifier screen completed in Drosophila linking PPT1 with genes involved in synaptic vesicle recycling, endosomal trafficking, and synaptic development [69, 70].…”

“…These alterations are supported by a gene modifier screen completed in Drosophila linking PPT1 with genes involved in synaptic vesicle recycling, endosomal trafficking, and synaptic development [69, 70]. Cholesterol metabolism was confirmed to be altered in Ppt1 −/− neurons both by upregulation of the rate of sterol synthesis [68] and by an increased uptake of apolipoprotein A-1 (apoA–I) [71]. Together, these studies indicate a potential dysfunction of neuronal–glia cell interactions during neuronal maturation and synaptogenesis in the developing PPT1-deficient brain [71].…”

Effect of Neurogranin Phosphorylation on Oxidative Stress by Hydrogen Peroxide in Early Onset of Batten Disease

“…영아형 바텐병(early onset of Batten disease, EBD)은 Ceroid 유전자의 산물인 Lipofuscinosis, Neuronal 1 (CLN1) palmi-의 toyl-protein thioesterase 1 (PPT1) 기능상실로 인해 신경 퇴 행 질환인 영아형 바텐병으로 유도되며 다양한 형태의 [12], 중에서도 가장 치명적이고 파괴적인 질병으로 인구 NCLs 명 당 명의 발병률과 명 중 명이 보인자 빈도를 보 10,000 1 70 1 이며 핀란드 사람에게서 많이 보고되고 출생 , [1,9,10,17,20,22], 후 약 개월 이내에 발병한다 영아형 바텐병은 리소좀 6~24 [4]. 에 라는 (lysosome) ceroid (thioesterified polypeptides) waste 가 비정상적으로 축적 되어지는 증상을 보인다 product 현재까지 다양한 연구 결과를 통해 영아형 바텐 [1,7,11,21,22]. 병 환자에서 효소의 불활성과 수송의 중단을 이끄는 다 PPT1 수의 및 들이 보고 되어 missense mutation nonsense mutation 졌다 [6,7,16,17,20].…”