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Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: a comprehensive review.

Venkatesan R, Ji E, Kim SY - Biomed Res Int (2015)

Bottom Line: Neurotrophins depletion accelerates the progression of AD and therefore, replacing such neurotrophins may be a potential treatment for neurodegenerative disease.Here, we review the phytochemicals that mediate the signaling pathways involved in neuroprotection specifically neurotrophin-mediated activation of Trk receptors and members of p75(NTR) superfamily.We focus on representative phenolic derivatives, iridoid glycosides, terpenoids, alkaloids, and steroidal saponins as regulators of neurotrophin-mediated neuroprotection.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Gachon University, No. 191, Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea.

ABSTRACT
Alzheimer's disease (AD), characterized by progressive dementia and deterioration of cognitive function, is an unsolved social and medical problem. Age, nutrition, and toxins are the most common causes of AD. However, currently no credible treatment is available for AD. Traditional herbs and phytochemicals may delay its onset and slow its progression and also allow recovery by targeting multiple pathological causes by antioxidative, anti-inflammatory, and antiamyloidogenic properties. They also regulate mitochondrial stress, apoptotic factors, free radical scavenging system, and neurotrophic factors. Neurotrophins such as BDNF, NGF, NT3, and NT4/5 play a vital role in neuronal and nonneuronal responses to AD. Neurotrophins depletion accelerates the progression of AD and therefore, replacing such neurotrophins may be a potential treatment for neurodegenerative disease. Here, we review the phytochemicals that mediate the signaling pathways involved in neuroprotection specifically neurotrophin-mediated activation of Trk receptors and members of p75(NTR) superfamily. We focus on representative phenolic derivatives, iridoid glycosides, terpenoids, alkaloids, and steroidal saponins as regulators of neurotrophin-mediated neuroprotection. Although these phytochemicals have attracted attention owing to their in vitro neurotrophin potentiating activity, their in vivo and clinical efficacy trials has yet to be established. Therefore, further research is necessary to prove the neuroprotective effects in preclinical models and in humans.

No MeSH data available.


Related in: MedlinePlus

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Mentions: Olea europaea, a member of the Oleaceae family, contains the polyphenolic compound oleuropein and is used as a traditional therapy and as a herbal tea; it has been reported to possess hypocholesterolemic, antioxidant, antihypertensive, antiatherogenic, anti-inflammatory, and hypoglycemic properties [128]. Oleuropein (Figure 12) decreased the level of GSH and increased NGF and BDNF levels in serum and elevated the level of NGF in olfactory lobes and the hypothalamus; additionally, it increased BDNF levels in the olfactory lobe but decreased levels of NGF/BDNF in the hippocampus and striatum. Oleuropein did not affect TrkA, TrkB, and P75 expression levels [87]. The antioxidant activity of oleuropein inhibits the aggregation of Aβ42 by reducing the appearance of toxic species in transgenic CL2006 and CL4176 strains of Caenorhabditis elegans [129]. Another study revealed that oleuropein aglycon hinders Aβ (1–42) aggregation and eliminates its cytotoxicity [130]. Additionally, the antiamyloidogenic effect of oleuropein was evidenced by a marked elevation of α-secretase with a significant reduction in Aβ oligomers in human neuroblastoma SK-N-SH cells [131]. There is evidence that supports phenolic compounds from olive oil crossing the BBB [132].


Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: a comprehensive review.

Venkatesan R, Ji E, Kim SY - Biomed Res Int (2015)

© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4446472&req=5

Mentions: Olea europaea, a member of the Oleaceae family, contains the polyphenolic compound oleuropein and is used as a traditional therapy and as a herbal tea; it has been reported to possess hypocholesterolemic, antioxidant, antihypertensive, antiatherogenic, anti-inflammatory, and hypoglycemic properties [128]. Oleuropein (Figure 12) decreased the level of GSH and increased NGF and BDNF levels in serum and elevated the level of NGF in olfactory lobes and the hypothalamus; additionally, it increased BDNF levels in the olfactory lobe but decreased levels of NGF/BDNF in the hippocampus and striatum. Oleuropein did not affect TrkA, TrkB, and P75 expression levels [87]. The antioxidant activity of oleuropein inhibits the aggregation of Aβ42 by reducing the appearance of toxic species in transgenic CL2006 and CL4176 strains of Caenorhabditis elegans [129]. Another study revealed that oleuropein aglycon hinders Aβ (1–42) aggregation and eliminates its cytotoxicity [130]. Additionally, the antiamyloidogenic effect of oleuropein was evidenced by a marked elevation of α-secretase with a significant reduction in Aβ oligomers in human neuroblastoma SK-N-SH cells [131]. There is evidence that supports phenolic compounds from olive oil crossing the BBB [132].

Bottom Line: Neurotrophins depletion accelerates the progression of AD and therefore, replacing such neurotrophins may be a potential treatment for neurodegenerative disease.Here, we review the phytochemicals that mediate the signaling pathways involved in neuroprotection specifically neurotrophin-mediated activation of Trk receptors and members of p75(NTR) superfamily.We focus on representative phenolic derivatives, iridoid glycosides, terpenoids, alkaloids, and steroidal saponins as regulators of neurotrophin-mediated neuroprotection.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Gachon University, No. 191, Hambakmoero, Yeonsu-gu, Incheon 406-799, Republic of Korea.

ABSTRACT
Alzheimer's disease (AD), characterized by progressive dementia and deterioration of cognitive function, is an unsolved social and medical problem. Age, nutrition, and toxins are the most common causes of AD. However, currently no credible treatment is available for AD. Traditional herbs and phytochemicals may delay its onset and slow its progression and also allow recovery by targeting multiple pathological causes by antioxidative, anti-inflammatory, and antiamyloidogenic properties. They also regulate mitochondrial stress, apoptotic factors, free radical scavenging system, and neurotrophic factors. Neurotrophins such as BDNF, NGF, NT3, and NT4/5 play a vital role in neuronal and nonneuronal responses to AD. Neurotrophins depletion accelerates the progression of AD and therefore, replacing such neurotrophins may be a potential treatment for neurodegenerative disease. Here, we review the phytochemicals that mediate the signaling pathways involved in neuroprotection specifically neurotrophin-mediated activation of Trk receptors and members of p75(NTR) superfamily. We focus on representative phenolic derivatives, iridoid glycosides, terpenoids, alkaloids, and steroidal saponins as regulators of neurotrophin-mediated neuroprotection. Although these phytochemicals have attracted attention owing to their in vitro neurotrophin potentiating activity, their in vivo and clinical efficacy trials has yet to be established. Therefore, further research is necessary to prove the neuroprotective effects in preclinical models and in humans.

No MeSH data available.


Related in: MedlinePlus