Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0752347 (Dementia with Lewy bodies)
 1,653 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the tuberous sclerosis complex (TSC) gene products, tuberin is assumed to be the functional component, being involved in a wide variety of cellular processes. Here, we report for the first time that tuberin dysfunction may represent a mechanism for neuronal damage in Alzheimer's disease (AD), Parkinson's disease with dementia (PD/DLB), and a mouse model of PD. Tuberin was hyperphosphorylated at Thr1462 in post-mortem frontal cortex tissue of both AD and PD/DLB patients and in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). Both PTEN and Akt phosphoactivation corresponded to the hyperphosphorylation patterns of tuberin suggesting that the PTEN-Akt pathway might be the mechanism of tuberin phosphorylation. Our data provide new information regarding the possible role of tuberin dysfunction in major neurodegenerative disorders, such as AD and PD, whereby inhibition of tuberin function may trigger an onset of neuronal cell death.
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PMID:Role of tuberin in neuronal degeneration. 1832 Mar 6

It has been nearly a decade since the first landmark studies implicating familial recessive Parkinson's disease genes in the regulation of selective mitochondrial autophagy. The PTEN-induced kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin (encoded by the PARK2 gene) act together to mark depolarized mitochondria for degradation. There is now an extensive body of literature detailing key mediators and steps in this pathway, based mostly on work in transformed cell lines. However, the degree to which PINK1-triggered mitophagy contributes to mitochondrial quality control in the mammalian brain, and the extent to which its disruption contributes to Parkinson's disease pathogenesis remain uncertain. In recent years, it has become clear that there are multiple, potentially redundant, pathways of cargo specification for mitophagy. Important mitophagy-independent functions of PINK1 and Parkin are also emerging. This review summarizes key features of three major mitophagy cargo recognition systems: receptor-mediated, ubiquitin-mediated and cardiolipin-mediated. New animal models that may be useful for tracking the delivery of mitochondria into lysosomes in different neuronal populations will be highlighted. Combining these research tools with methods to selectively disrupt specific mitophagy pathways may lead to a better understanding of the potential role of mitophagy in modulating neuronal vulnerability in Parkinson's spectrum (PD/PDD/DLB) and other neurodegenerative diseases.
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PMID:Multiple pathways for mitophagy: A neurodegenerative conundrum for Parkinson's disease. 2962 47