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1.  Cerebrospinal Fluid Levels of sAPPα and sAPPβ in Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates 
We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPα sAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPα and sAPPβ levels between the groups. Significant correlations were observed between sAPPα and sAPPβ and between sAPPβ and Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPα and sAPPβ levels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPα correlated with p-Tau and sAPPβ with Aβ40. The differential association between sAPPα and sAPPβ with Aβ and Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.
PMCID: PMC3182340  PMID: 21966597
2.  Identification of Novel α-Synuclein Isoforms in Human Brain Tissue by using an Online NanoLC-ESI-FTICR-MS Method 
Neurochemical Research  2011;36(11):2029-2042.
Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB) are neurodegenerative diseases that are characterized by intra-neuronal inclusions of Lewy bodies in distinct brain regions. These inclusions consist mainly of aggregated α-synuclein (α-syn) protein. The present study used immunoprecipitation combined with nanoflow liquid chromatography (LC) coupled to high resolution electrospray ionization Fourier transform ion cyclotron resonance tandem mass spectrometry (ESI-FTICR-MS/MS) to determine known and novel isoforms of α-syn in brain tissue homogenates. N-terminally acetylated full-length α-syn (Ac-α-syn1–140) and two N-terminally acetylated C-terminally truncated forms of α-syn (Ac-α-syn1–139 and Ac-α-syn1–103) were found. The different forms of α-syn were further studied by Western blotting in brain tissue homogenates from the temporal cortex Brodmann area 36 (BA36) and the dorsolateral prefrontal cortex BA9 derived from controls, patients with DLB and PD with dementia (PDD). Quantification of α-syn in each brain tissue fraction was performed using a novel enzyme-linked immunosorbent assay (ELISA).
PMCID: PMC3183298  PMID: 21674238
Cerebrospinal fluid; Immunoprecipitation; Neurodegenerative diseases; Mass spectrometry; Synuclein
3.  Inhibition of acetylcholine muscarinic M1 receptor function by the M1-selective ligand muscarinic toxin 7 (MT-7) 
British Journal of Pharmacology  2000;131(3):447-452.
MT-7 (1–30 nM), a peptide toxin isolated from the venom of the green mamba Dendroaspis angusticeps and previously found to bind selectively to the muscarinic M1 receptor, inhibited the acetylcholine (ACh)-stimulated [35S]-guanosine-5′-O-(3-thio)triphosphate ([35S]-GTPγS) binding to membranes of Chinese hamster ovary (CHO) cells stably expressing the cloned human muscarinic M1 receptor subtype.MT-7 failed to affect the ACh-stimulated [35S]-GTPγS binding in membranes of CHO cells expressing either the M2, M3 or M4 receptor subtype.In N1E-115 neuroblastoma cells endogenously expressing the M1 and M4 receptor subtypes, MT-7 (0.3–3.0 nM) inhibited the carbachol (CCh)-stimulated inositol phosphates accumulation, but failed to affect the CCh-induced inhibition of pituitary adenylate cyclase activating polypeptide (PACAP) 38-stimulated cyclic AMP accumulation.In both CHO/M1 and N1E-115 cells the MT-7 inhibition consisted in a decrease of the maximal agonist effect with minimal changes in the agonist EC50 value.In CHO/M1 cell membranes, MT-7 (0.05–25 nM) reduced the specific binding of 0.05, 1.0 and 15 nM [3H]-N-methylscopolamine ([3H]-NMS) in a concentration-dependent manner, but failed to cause a complete displacement of the radioligand. Moreover, MT-7 (3 nM) decreased the dissociation rate of [3H]-NMS by about 5 fold.CHO/M1 cell membranes preincubated with MT-7 (10 nM) and washed by centrifugation and resuspension did not recover control [3H]-NMS binding for at least 8 h at 30°C.It is concluded that MT-7 acts as a selective noncompetitive antagonist of the muscarinic M1 receptors by binding stably to an allosteric site.
PMCID: PMC1572361  PMID: 11015294
Dendroaspis angusticeps toxin; muscarinic receptor subtypes; [35S]-GTPγS binding; phosphoinositide hydrolysis; cyclic AMP accumulation; [3H]-NMS binding; Chinese hamster ovary cells; N1E-115 cells; noncompetitive antagonism

Results 1-3 (3)