Positive Allosteric Modulators of Trk Receptors for the Treatment of Alzheimer's Disease.

Neurotrophins are important regulators of neuronal and non-neuronal functions. As such, the neurotrophins and their receptors, the tropomyosin receptor kinase (Trk) family of receptor tyrosine kinases, has attracted intense research interest and their role in multiple diseases including Alzheimer's disease has been described. Attempts to administer neurotrophins to patients have been reported, but the clinical trials have so far have been hampered by side effects or a lack of clear efficacy.

Neuroprotective and Disease-Modifying Effects of the Triazinetrione ACD856, a Positive Allosteric Modulator of Trk-Receptors for the Treatment of Cognitive Dysfunction in Alzheimer's Disease.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer's disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect can possibly increase over time, there is still a need for alternative treatments that will improve cognitive function in patients with AD.

Antidepressant effects of novel positive allosteric modulators of Trk-receptor mediated signaling - a potential therapeutic concept?

Background: Major depressive disorder (MDD) is defined as a complex mental disorder which is characterized by a pervasive low mood and aversion to activity. Several types of neurotransmitter systems e.g.

Neurotrophin-targeted therapeutics: A gateway to cognition and more?

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), are small proteins expressed in the brain and peripheral tissues, which regulate several key aspects of neuronal function, including neurogenesis, synaptic plasticity and neuroprotection, but also programmed cell death. This broad range of effects is a result of a complex downstream signaling pathway, with differential spatial and temporal activation patterns further diversifying their physiological effects. Alterations in neurotrophin levels, or known polymorphisms in neurotrophin genes, have been linked to a variety of disorders, including depression and Alzheimer's disease (AD).

Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and results in severe neurodegeneration and progressive cognitive decline. Neurotrophins are growth factors involved in the development and survival of neurons, but also in underlying mechanisms for memory formation such as hippocampal long-term potentiation. Our aim was to identify small molecules with stimulatory effects on the signaling of two neurotrophins, the nerve growth factor (NGF) and the brain derived neurotrophic factor (BDNF).