Current Alzheimer Research - Volume 3, Issue 1, 2006

Current Alzheimer Research enters the third year of successful publication with a great sense of satisfaction and accomplishment. All five issues of its second volume were completed and published on time, as promised. The second volume featured a total of 65 articles, a 100% jump from its previous volume. These articles, which are comprised of primary research and review work, were written by experts in the field of Alzhe Read More

The discovery of small molecules capable of promoting neurogenesis will contribute to the elucidation of the physiological roles of neurogenesis and to novel therapeutic approaches. Small molecule development can be targeted to the promotion of precursor proliferation, survival, migration or maturation and might be applied to augmenting physiological neurogenesis already present in the dentate gyrus or subventricular zo Read More

Herein, we present data to support a preclinical proof of concept for the therapeutic potential of allopregnanolone to promote neurogenesis. Our recent work has demonstrated that the neuroactive progesterone metabolite, allopregnanolone (3α-hydroxy-5α-pregnan-20-one), (APα) induced, in a dose dependent manner, a significant increase in proliferation of neuroprogenitor cells (NPCs) derived from the rat hippocampus and Read More

The neurotrophins mediate diverse actions in the developing peripheral and central nervous systems. They are initially synthesized as precursor forms, or proneurotrophins, that are cleaved to release C-terminal mature forms that bind to Trk receptor tyrosine kinases to enhance synaptic plasticity and neuronal survival. Recent studies suggest that proneurotrophins are not inactive precursors, but signaling proteins that ca Read More

Neurogenesis, or the production of new neurons from neuronal precursor cells, is a normal phenomenon in the adult brain, and is accentuated by brain injury. Forms of injury associated with increased neurogenesis include both acute (e.g., stroke) and chronic neurodegenerations. Studies on human postmortem material and transgenic mice overexpressing amyloid precursor protein mutations found in familial Alzheimer's dise Read More

Rodents housed in an enriched environment, exercise by running or perform learning and memory tasks show an increase in hippocampal neurogenesis. We show that both environmental enrichment, as well as performance in the Morris water maze, a hippocampal-dependent learning task, leads to an increase in local VEGF expression in rats. We genetically recreated this situation by somatic cell gene transfer using rec Read More

Studies on oligodendrocytes, the myelin-forming cells of the central nervous system, and on the progenitor cells from which they are derived, have provided several novel insights into the role of intracellular redox state in cell function. A central unifying theme of this research is that redox state modulation lies at the heart of understanding cellintrinsic aspects of precursor cell function, responsiveness of precursor cells to cell-ext Read More

Age is the biggest risk factor for the development of neurodegenerative diseases. Consequently, as the population ages it becomes more critical to find ways to avoid the debilitating cost of neurodegenerative diseases such as Alzheimer's. Some of the non-invasive strategies that can potentially slow down the mental decline associated with aging are exercise and use of multi-sensory environmental stimulation. The beneficial effe Read More

Many researchers have questioned whether new potential therapies aimed at reversing Alzheimer's disease (AD) are indeed scientifically feasible. A number of approved therapies already exist for Alzheimer's disease, yet these drugs only slow the disease progression for a period of time and treat the symptoms of this devastating disease. New therapies intended to reverse the disease would necessarily need to replace dead, Read More

The remediation of neurodegeneration and cognitive decline in Alzheimer's Disease (AD) remains a challenge to basic scientists and clinicians. It has been suggested that adult bone marrow stem cells can transdifferentiate into different neuronal phenotypes. Here we demonstrate that the a-secretase-cleaved fragment of the amyloid precursor protein (sAPPα), a potent neurotrophic factor, potentiates the nerve growth factor Read More

After much initial debate for and against the role of amyloid in Alzheimer's disease (AD), mutations on the amyloid precursor protein (APP) and processing pathways that increase levels of the amyloid b peptide of 42 residues (Aβ42) have established that faulty function or processing of these proteins are responsible for AD pathogenesis. Given the neurotoxicity of aggregates of Ab42, the central role of this peptide in AD patho Read More

Alzheimer disease (AD) is a devastating condition and patients, caregivers, clinicians, and scientists are eager to decipher the underlying disease mechanism and, thereafter, target this therapeutically. Most investigators studying the underlying cause of AD have focused on amyloid-β (Aβ) such that the Amyloid Cascade Hypothesis is the predominant mechanism thought to be responsible for the disease. However, a number of c Read More

The amyloid hypothesis has dominated the thinking in our attempts to understand, diagnose and develop drugs for Alzheimer's disease (AD). This article presents a new hypothesis that takes into account the numerous familial AD (FAD) mutations in the amyloid precursor protein (APP) and its processing pathways, but suggests a new perspective beyond toxicity of forms of the amyloid β-peptide (Abgr;). Clearly, amyloid deposit Read More