Age-related macular degeneration (AMD) and Alzheimer's disease (AD) are neurodegenerative conditions that afflict millions of elderly people around the world. AMD is a progressive retinal disorder tha Show more
Age-related macular degeneration (AMD) and Alzheimer's disease (AD) are neurodegenerative conditions that afflict millions of elderly people around the world. AMD is a progressive retinal disorder that leads to central vision loss whereas AD primarily causes cognitive decline and behavioral changes. While each disease has distinct clinical manifestations, the accumulation of extracellular amyloid-β is a common histopathologic finding. Similarly, cerebral amyloid angiopathy (CAA), a vascular condition that can exist independent or with AD, is characterized by the accumulation of amyloid-β in cerebral blood vessels. While significant investigation of the pathophysiologic links between AMD and AD has been conducted, the underlying similarities and differences in the pathobiology of AMD and CAA has not been considered. In this review, we discuss the common pathological features of these two conditions. We then discuss the similar pathobiology that involves cholesterol metabolism, apolipoprotein E, amyloid-β, and complement mediated inflammation. At the same time, we discuss key differences in their pathobiology. This discussion sheds new perspective and insights of their pathobiology. Show less
Pilocytic astrocytoma (PA) is the most common primary brain tumor in children; various signaling pathways have been implicated in its biology. The Notch signaling pathway has been found to play a role Show more
Pilocytic astrocytoma (PA) is the most common primary brain tumor in children; various signaling pathways have been implicated in its biology. The Notch signaling pathway has been found to play a role in the development, stem cell biology, and pathogenesis of several cancers, but its role in PA has not been investigated. We studied alterations in Notch signaling components in tumor tissue from 18 patients with PA and 4 with other low-grade astrocytomas to identify much needed therapeutic targets. We found that Notch pathway members were overexpressed at the mRNA (NOTCH1, NOTCH2, HEY1, HEY2) and protein (HES1) levels in PAs at various anatomic sites compared with non-neoplastic brain samples. These changes were not associated with specific BRAF alterations. Inhibiting the Notch pathway in the pediatric low-grade astrocytoma cell lines Res186 and Res259 using either RNA interference or a γ-secretase inhibitor resulted in variable, but significant, reduction in cell growth and migration. This study suggests a potential role for Notch signaling in pediatric low-grade astrocytoma tumorigenesis and that Notch signaling may be a viable pathway therapeutic target. Show less