1.Method development for the determination of D- and L-isomers of leucine in human plasma by high-performance liquid chromatography tandem mass spectrometry and its application to animal plasma samples.
Sugimoto H1, Kakehi M2, Jinno F2. Anal Bioanal Chem. 2015 Oct;407(26):7889-98. doi: 10.1007/s00216-015-8999-1. Epub 2015 Sep 7.
We developed a highly sensitive and specific high-performance liquid chromatography tandem mass spectrometry method with an electrospray ionization for the determination of D- and L-isomers of leucine in human plasma. Phosphate-buffered saline was used as the surrogate matrix for preparation of calibration curves and quality control samples. The extraction of D- and L-leucine in plasma samples (100 μL) was performed using cationic exchange solid-phase extraction. The enantiomer separation of D- and L-leucine was successfully achieved without derivatization using a CHIRALPAK ZWIX(-) with an isocratic mobile phase comprised of methanol/acetonitrile/1 mol/L ammonium formate/formic acid (500:500:25:2, v/v/v/v) at a flow rate of 0.5 mL/min. In addition, the discrimination of DL-leucine from structural isomers DL-isoleucine and DL-allo-isoleucine was performed using the unique precursor and product ion pair transition of DL-leucine (m/z 132.1 > 43.
2.Acetyl-DL-leucine improves gait variability in patients with cerebellar ataxia-a case series.
Schniepp R1, Strupp M1, Wuehr M2, Jahn K3, Dieterich M1, Brandt T4, Feil K1. Cerebellum Ataxias. 2016 Apr 12;3:8. doi: 10.1186/s40673-016-0046-2. eCollection 2016.
Acetyl-DL-leucine is a modified amino acid that was observed to improve ataxic symptoms in patients with sporadic and hereditary forms of ataxia. Here, we investigated the effect of the treatment with Acetyl-DL-leucine on the walking stability of patients with cerebellar ataxia (10x SAOA, 2x MSA-C, 2x ADA, 1x CACNA-1A mutation, 2x SCA 2, 1x SCA 1). Treatment with Acetyl-DL-leucine (500 mg; 3-3-4) significantly improved the coefficient of variation of stride time in 14 out of 18 patients. Moreover, subjective ambulatory scores (FES-I and ABC) and the SARA scores were also improved under treatment. Further prospective studies are necessary to support these class III observational findings.
3.Nutritional Supplementation with Essential Amino Acids and Phytosterols May Reduce Risk for Metabolic Syndrome and Cardiovascular Disease in Overweight Individuals with Mild Hyperlipidemia.
Coker RH1, Deutz NE2, Schutzler S3, Beggs M4, Miller S3, Wolfe RR3, Wei J3. J Endocrinol Diabetes Obes. 2015;3(2). pii: 1069. Epub 2015 Apr 15.
BACKGROUND: Hyperlipidemia and insulin resistance are risk factors for the development of metabolic syndrome and cardiovascular disease. We have previously observed that supplementation with essential amino acids (EAA) could lower plasma triglycerides, and may improve glucose metabolism.
4.The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway.
Imai Y1, Kobayashi Y2, Inoshita T1, Meng H3, Arano T1, Uemura K4, Asano T4, Yoshimi K5, Zhang CL2, Matsumoto G6, Ohtsuka T7, Kageyama R7, Kiyonari H8, Shioi G8, Nukina N6, Hattori N9, Takahashi R2. PLoS Genet. 2015 Sep 10;11(9):e1005503. doi: 10.1371/journal.pgen.1005503. eCollection 2015.
Leucine-rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of familial and idiopathic Parkinson's disease (PD). We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor-like protein with six repeated Neuralized domains, NEURL4. LRRK2 binds to NEURL4 and HERC2 via the LRRK2 Ras of complex proteins (ROC) domain and NEURL4, respectively. HERC2 and NEURL4 link LRRK2 to the cellular vesicle transport pathway and Notch signaling, through which the LRRK2 complex promotes the recycling of the Notch ligand Delta-like 1 (Dll1)/Delta (Dl) through the modulation of endosomal trafficking. This process negatively regulates Notch signaling through cis-inhibition by stabilizing Dll1/Dl, which accelerates neural stem cell differentiation and modulates the function and survival of differentiated dopaminergic neurons. These effects are strengthened by the R1441G ROC domain-mutant of LRRK2. These findings suggest that the alteration of Notch signaling in mature neurons is a component of PD etiology linked to LRRK2.
