Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease.

Neuropeptide Y (NPY) is one of the most abundant protein transmitters in the central nervous system with roles in a variety of biological functions including: food intake, cardiovascular regulation, cognition, seizure activity, circadian rhythms, and neurogenesis. Reduced NPY and NPY receptor expression is associated with numerous neurodegenerative disorders including Alzheimer disease (AD). To determine whether replacement of NPY could ameliorate some of the neurodegenerative and behavioral pathology associated with AD, we generated a lentiviral vector expressing NPY fused to a brain transport peptide (apoB) for widespread CNS delivery in an APP-transgenic (tg) mouse model of AD.

ptr-MIR169 is a posttranscriptional repressor of PtrHAP2 during vegetative bud dormancy period of aspen (Populus tremuloides) trees.

Dormancy is a mechanism evolved in woody perennial plants to survive the winter freezing and dehydration stress via temporary suspension of growth. We have identified two aspen microRNAs (ptr-MIR169a and ptr-MIR169h) which were highly and specifically expressed in dormant floral and vegetative buds. ptr-MIR169a and its target gene PtrHAP2-5 showed inverse expression patterns during the dormancy period.

Peripheral delivery of a CNS targeted, metalo-protease reduces aβ toxicity in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD), an incurable, progressive neurodegenerative disorder, is the most common form of dementia. Therapeutic options have been elusive due to the inability to deliver proteins across the blood-brain barrier (BBB). In order to improve the therapeutic potential for AD, we utilized a promising new approach for delivery of proteins across the BBB.

Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson's and Lewy body diseases.

Accumulation of the synaptic protein alpha-synuclein (alpha-syn) is a hallmark of Parkinson's disease (PD) and Lewy body disease (LBD), a heterogeneous group of disorders with dementia and parkinsonism, where Alzheimer's disease and PD interact. Accumulation of alpha-syn in these patients might be associated with alterations in the autophagy pathway. Therefore, we postulate that delivery of beclin 1, a regulator of the autophagy pathway, might constitute a strategy toward developing a therapy for LBD/PD.

Neuropeptide Y fragments derived from neprilysin processing are neuroprotective in a transgenic model of Alzheimer's disease.

The endopeptidase neprilysin (NEP) is a major amyloid-beta (Abeta) degrading enzyme and has been implicated in the pathogenesis of Alzheimer's disease. Because NEP cleaves substrates other than Abeta, we investigated the potential role of NEP-mediated processing of neuropeptides in the mechanisms of neuroprotection in vivo. Overexpression of NEP at low levels in transgenic (tg) mice affected primarily the levels of neuropeptide Y (NPY) compared with other neuropeptides.

Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice.

Background: Proteolytic degradation has emerged as a key pathway involved in controlling levels of the Alzheimer's disease (AD)-associated amyloid-beta (Abeta) peptide in the brain. The endopeptidase, neprilysin, has been implicated as a major Abeta degrading enzyme in mice and humans. Previous short and intermediate term studies have shown the potential therapeutic application of neprilysin by delivering this enzyme into the brain of APP transgenic mice using gene transfer with viral vectors.