Disease relevance of Appl

• Recently it was shown that A beta aggregates induce neuronal cell death via beta-amyloid peptide-binding protein (BBP), a receptor for A beta in BBP-transfected cells, which is known to be sensitive to pertussis toxin, a G alpha(i/o) family inhibitor [1].
• Alzheimer's disease is a neurodegenerative disorder related to the formation of protein aggregates. beta-Amyloid protein (A beta), generated by enzymatic cleavage of amyloid precursor protein (APP), can cause such aggregation, and these aggregates may cause neuronal cell death by inducing apoptosis [1].

Psychiatry related information on Appl

• In addition, the degenerative phenotype of loe is enhanced by a mutation in amyloid precursor protein-like (APPL), the fly homolog of the human amyloid precursor protein involved in Alzheimer's disease [2].
• A missense mutation has been found in the gene encoding the GABA-A beta 3 subunit in a patient with chronic insomnia [3].

High impact information on Appl

• Deletion of the C terminus of APP695 or APPL, including the kinesin binding region, disrupted axonal transport of APP695 and APPL and abolished the organelle accumulation phenotype [4].
• Drosophila amyloid precursor protein-like (Appl) gene encodes a protein product (APPL) similar to beta-amyloid precursor protein (APP) associated with Alzheimer's disease [5].
• We show that a fast phototaxis defect in Appl- flies is partially rescued by transgenes expressing the wild-type, but not a mutant, APPL protein [5].
• The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and Appl processing [2].
• APPL-induced apoptosis is rescued by overexpression of dAPP-BP1 [6].

Biological context of Appl

• The Appl transcript spans approximately 38 kb (1 kb = 10(3) base-pairs) of genomic DNA [7].
• Appl defines a new locus within the 1B division of the X-chromosome, a region previously shown to be important for neural development [7].
• In this paper, we compare the Appl gene expression with the pattern of expression of the beta-amyloid protein precursor (APP) gene in mammals [7].
• Electrophysiologically, A-type K+ current was significantly enhanced, and spontaneous excitatory postsynaptic potentials (sEPSPs) were greatly increased in APPL mutants lacking sAPPL [8].
• The dinucleotide-binding consensus sequence and beta 1-alpha A-beta 2, Rossmann fold structure, and beta-sheet structures are completely conserved from mammals to insect [9].

Anatomical context of Appl

• We present in situ RNA localization data that demonstrate that the Appl transcript is found in post-mitotic neurons in all developmental stages, in the central and peripheral nervous systems [7].
• APPL immunoreactivity was observed in neuronal cell bodies, axonal tracts, and neuropil regions [10].
• A key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of senile plaques consisting largely of a peptide known as beta-amyloid (Abeta) that is derived from the amyloid precursor protein (APP) [11].
• Double-labeling experiments with different neuronal markers were used to distinguish between APPL associated with neuronal processes or extracellular matrix [12].
• Interestingly, in adult brains, APPL protein is enriched in the mushroom bodies and to a lesser extent in the central complex, structures involved in learning and memory [12].

Associations of Appl with chemical compounds

• The phosphotyrosine interaction domain of APLIP1 interacts with a sequence containing GYENPTY in the cytoplasmic domain of APPL [13].
• The findings suggests that the Cu(II)-binding equilibrium at the phylogenetic stage of Drosophila APPL and C. elegans APL-1 is shifted from the exchangeable Cu(II) pool to the tightly bound, nonexchangeable pool and that ancestral CuBDs may exert antioxidation activities in vivo [14].

References