Advances in small molecules promoting neurotrophic function

Price, Raymond D.; Milne, Stuart; Sharkey, John; Matsuoka, Naoki

doi:10.1016/j.pharmthera.2007.03.005

Cited by 133 publications

(83 citation statements)

References 149 publications

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“…In addition, drugs directly targeting the stimulation of BDNF cascades (i.e. small molecules BDNF) have also being developed and can be an interesting disease-modifying treatment option for Alzheimer's disease (Price et al 2007;Longo et al 2007;Massa et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Alzheimer’s Disease: Physiopathology and Beyond

2011

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Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF became a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have reported altered levels of BDNF in the circulation, i.e. serum or plasma, of patients with Alzheimer's disease (AD), and low BDNF levels in the CSF as predictor of future cognitive decline in healthy older subjects. Altered BDNF circulating levels have also been reported in other neurodegenerative and psychiatric disorders, hampering its use as a specific biomarker for AD. Therefore, BDNF seems to be an unspecific biomarker of neuropsychiatric disorders marked by neurodegenerative changes.

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Section: Discussionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Alzheimer’s Disease: Physiopathology and Beyond

2011

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“…However, there are major caveats to targeting BDNF, such as the fact that levels of BDNF are maintained within an optimal range in neurons and also because each disease seems to be associated with brainregion-specific alterations in BDNF. For example, therapies that increase or decrease BDNF levels or signaling activity outside this range, or in incorrect neural circuit regions, may lead to neuronal excitotoxicity, undesired increased growth or survival of tumor cells, or cardiovascular side effects (Price et al, 2007). Another drawback to use of chemical modulators of BDNF signaling is the lack of mechanistic insight into their ability to increase BDNF.…”

Section: Brain-derived Neurotrophicmentioning

confidence: 99%

“…Another drawback to use of chemical modulators of BDNF signaling is the lack of mechanistic insight into their ability to increase BDNF. As noted in sections II.A and IV.A, many therapies for schizophrenia and depression have indirect effects on BDNF levels (Price et al, 2007), although the mechanism for this modulation is unknown. Furthermore, the use of recombinant BDNF molecules has not been successful in clinical trials because of side effects (Chao et al, 2006), inability to cross the blood-brain barrier with systemic treatment, and complications associated with surgical infusion of proteins directly into the brain (Monteggia, 2011).…”

Section: Brain-derived Neurotrophicmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders

Autry

Monteggia²

2012

Pharmacol Rev

1,193

764

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“…[14][15][16] To avoid the side effects, development of orally active small molecules that potentiate the expression and activity of NGF is warranted. 17,18) The extracts of plants from the Dioscorea genus were reported to exhibit hypoglycemic, 19) immunostimulatory, 20) and anti-inflammatory effects, 21) as well as anti-tumor 22) and anti-osteoporotic activity. 23) Dioscorea japonica THUNBERG.…”

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confidence: 99%