15-Lipoxygenase-Mediated Lipid Peroxidation Regulates LRRK2 Kinase Activity.

Mutations in that increase its kinase activity are strongly linked to genetic forms of Parkinson's disease (PD). However, the regulation of endogenous wild-type (WT) LRRK2 kinase activity remains poorly understood, despite its frequent elevation in idiopathic PD (iPD) patients. Various stressors such as mitochondrial dysfunction, lysosomal dyshomeostasis, or vesicle trafficking deficits can activate WT LRRK2 kinase, but the specific molecular mechanisms are not fully understood.

Evidence that enzyme processivity mediates differential Aβ production by PS1 and PS2.

The γ-secretase complex cleaves the carboxy-terminal 99 residue (C99) fragment of the amyloid precursor protein (APP) to generate the amyloid-β (Aβ) peptide. The catalytic activity of this complex is mediated either by the presenilin- 1 (PS1) or the presenilin-2 (PS2) subunit. In vitro and in vivo studies have demonstrated that PS1-containing complexes generate more total Aβ product than PS2-containing complexes, indicating greater cleavage activity by PS1- containing γ-secretase complexes at the APP γ-site.

Lysine 624 of the amyloid precursor protein (APP) is a critical determinant of amyloid β peptide length: support for a sequential model of γ-secretase intramembrane proteolysis and regulation by the amyloid β precursor protein (APP) juxtamembrane region.

γ-Secretase is a multiprotein intramembrane cleaving aspartyl protease (I-CLiP) that catalyzes the final cleavage of the amyloid β precursor protein (APP) to release the amyloid β peptide (Aβ). Aβ is the primary component of senile plaques in Alzheimer's disease (AD), and its mechanism of production has been studied intensely. γ-Secretase executes multiple cleavages within the transmembrane domain of APP, with cleavages producing Aβ and the APP intracellular domain (AICD), referred to as γ and ε, respectively.

The serum response factor and a putative novel transcription factor regulate expression of the immediate-early gene Arc/Arg3.1 in neurons.

The immediate-early effector gene Arc/Arg3.1 is robustly upregulated by synaptic activity associated with learning and memory. Here we show in primary cortical neuron culture that diverse stimuli induce Arc expression through new transcription.