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BACKGROUND In preclinical studies, davunetide promoted microtubule stability and reduced tau phosphorylation. Because progressive supranuclear palsy (PSP) is linked to tau pathology, davunetide could be a treatment for PSP. We assessed the safety and efficacy of davunetide in patients with PSP. METHODS In a double-blind, parallel group, phase 2/3 trial,(More)
Ac-208 is a plastocyanin-deficient mutant of Chlamydomonas reinhardtii that contains only 2-3% of the wild-type level of plastocyanin-encoding mRNA and no detectable plastocyanin. Sequence analysis of the ac-208 plastocyanin-encoding gene reveals a single nucleotide insertion in the first exon compared with the wild-type gene; this alters the reading frame(More)
AL-108 is the intranasal formulation of NAP (a peptide of eight amino acids, NAPVSIPQ). Phase IIa clinical results have recently shown that AL-108 has a positive impact on memory function in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease (AD). The clinical development of AL-108 has been based on extensive studies(More)
The current criteria for classification of Alzheimer's disease (AD) have deficiencies that limit drug development, research, and practice. The current standard for the clinical diagnosis of AD, the National Institute of Neurological and Communicative Disorders and Stroke (now known as the National Institute of Neurological Disorders and Stroke), and the(More)
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined(More)
A series of isoflavone and tyrphostin compounds were found to inhibit the degradation of cAMP by several cyclic nucleotide phosphodiesterase (PDE) isozymes. Specific hydroxyl groups on the isoflavone structure were critical for PDE isozyme-selective inhibition. Replacement of the C-7 hydroxyl group of the isoflavone with a methoxy group raised the IC(50)(More)
Activity-dependent neuroprotective protein (ADNP) is essential for brain formation. Peptide activity scanning identified NAP (NAPVSIPQ) as a small active fragment of ADNP that provides neuroprotection at very low concentrations. In cell culture, NAP has demonstrated protection against toxicity associated with the beta-amyloid peptide, N-methyl-D-aspartate,(More)
In a neural cell line, the secretion of excitatory amino acids in response to a depolarizing stimulus is potentiated by the addition of serotonin. The duration of this potentiation is dependent on the strength of the stimulus. Persistent secretory potentiation induced by a strong stimulus requires the activation of both serotonin and NMDA receptors.(More)
The phosphodiesterase activity in the HT4.7 neural cell line was pharmacologically characterized, and phosphodiesterase isozyme 4 (PDE4) was found to be the predominant isozyme. The Km for cAMP was 1-2 microM, indicative of a "low Km" phosphodiesterase, and the activity was inhibited by PDE4-selective inhibitors rolipram and Ro20-1724, but not PDE3- or(More)
Abnormal accumulation of α-synuclein is associated with several neurodegenerative disorders (synucleinopathies), including sporadic Parkinson's disease (PD). Genetic mutations and multiplication of α-synuclein cause familial forms of PD and polymorphisms in the α-synuclein gene are associated with PD risk. Overexpression of α-synuclein can impair essential(More)