Monoamine Oxidase-B Inhibition in Alzheimer's Disease

Riederer, Peter; Danielczyk, W; Grünblatt, Edna

doi:10.1016/s0161-813x(03)00106-2

Cited by 233 publications

(148 citation statements)

References 85 publications

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…Pharmacological studies have demonstrated that MAO inhibitors exert neuroprotective effects in patients with AD (21,52,53) through the following mechanisms: Improvement of cognitive impairment (50,54,55); antioxidant and enhancement of iron chelating activities (56-59); regulation of APP and Aβ expression processing (56,60), involving the activation of certain signaling pathways, including the p42/44 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signaling pathways (61); and inhibition of cholinesterase (ChE) activity (62-64).…”

Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 99%

“…An increasing number of molecular biology and pharmacology studies have shown the neuroprotective effects of MAO inhibitors on the prevention and treatment of AD (21,52,53) (Table I) (15,56,57,61,62,112,114,(131)(132)(133)(134)(135)(136)(137)(138)(139)(140)(141)(142)(143)(144). The main neuroprotective mechanisms of MAO inhibitors in AD include the following: i) Improvement of cognitive impairment (50,54,55), where MAO inhibitors correct chemical imbalances in the brain; ii) antioxidant activities and enhancement of iron-chelating activities (56)(57)(58)(59), where chelators can modulate Aβ accumulation, protect against tau hyperphosphorylation and block metal-associated oxidative stress, thereby holding considerable promise as effective anti-AD drugs (145,146); iii) regulation of APP and Aβ expression processing (56,60), for example ladostigil (TV3326), a selective MAO-B inhibitor, which regulates APP translation and processing (114); iv) the selective MAO inhibitors selegiline and rasagiline have been proven to possess neuroprotective activities in cell cultures and animal models of neurodegenerative diseases through the activation of certain signaling pathways, including p42/44 MAPK and PKC (61); v) inhibition of ChE activity by the MAO inhibitor rasagiline (62)(63)…”

Section: Evidence For the Neuroprotective Effect Of Mao Inhibitors In Admentioning

confidence: 99%

See 1 more Smart Citation

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Cai

2014

Molecular Medicine Reports

180

View full text Add to dashboard Cite

Abstract. Activated monoamine oxidase (MAO) has a critical role in the pathogenesis of Alzheimer's disease (AD), including the formation of amyloid plaques from amyloid β peptide (Aβ) production and accumulation, formation of neurofibrillary tangles, and cognitive impairment via the destruction of cholinergic neurons and disorder of the cholinergic system. Several studies have indicated that MAO inhibitors improve cognitive deficits and reverse Aβ pathology by modulating proteolytic cleavage of amyloid precursor protein and decreasing Aβ protein fragments. Thus, MAO inhibitors may be considered as promising therapeutic agents for AD.

show abstract

Section: Involvement Of Mao In Neurodegenerationmentioning

confidence: 99%

Section: Evidence For the Neuroprotective Effect Of Mao Inhibitors In Admentioning

confidence: 99%

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Cai

2014

Molecular Medicine Reports

180

View full text Add to dashboard Cite

show abstract

“…Not only an impairment of INSR leads to an activation of GSK3β as explained before, also oxidative stress can enhance the activity of this kinase (Hernandez and Avila, 2008). In 2004, Riederer et al already reviewed the link between oxidative stress and AD, especially regarding the increased MAO-B activity (Riederer et al, 2004). MAO-B is a flavin containing enzyme localized in the outer mitochondrial membrane and is responsible for the oxidative deamination of neurotransmitters (noradrenaline, dopamine and serotonin) and exogenous amines.…”

Section: Discussionmentioning

confidence: 98%

“…(Zhao et al, 2009). MAO-B activity is significantly increased in AD patients (Gotz et al, 1998;Grünblatt et al, 2005) and inhibition of MAO-B has a neuroprotective effects for AD (reviewed in (Riederer et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Different effects of soluble and aggregated amyloid β42 on gene/protein expression and enzyme activity involved in insulin and APP pathways

et al. 2012

View full text Add to dashboard Cite

Although Alzheimer's dementia (AD) is not characterised any longer simply as the accumulation and deposition of amyloid beta (A ) peptides and hyperphosphorylation of tau proteins within the brain, excessive A (42) deposition is still considered to play a major role in this illness. A are able to adopt many differently aggregate forms, including amyloid fibrils as well as nonfibrillar structures (soluble A (42) oligomers). It is not well-established that which A (42) state is most responsible for AD or why. We wanted to verify which effects A (42) oligomers and aggregated peptides have on gene expression, protein level and enzyme activity of insulin and amyloid precursor protein (APP) pathways in vitro. Human neuroblastoma cells (SH-SY5Y) were treated with varying concentrations of soluble and aggregated A (42). Treatment effects on -secretase (BACE), glycogen synthase kinase 3 (GSK3 ), glycogen synthase kinase 3 (GSK3 ), phosphatidylinositol-3 kinase (PI-3K), insulin-degrading enzyme (IDE), insulin-receptor substrate 1 (IRS1), insulin receptor (INSR) and monoamine oxidase B (MAO-B) were investigated via quantitative-PCR, western blot, ELISA and enzyme activity assay. We could find different effects of soluble and aggregated peptides especially on gene/protein expression of GSK3 and INSR and on GSK3 and MAO-B activity. Soluble peptides showed significant effects leading to increased gene expression and protein amount of GSK3 and to decreased level of gene and protein expression of INSR. MAO-B activity was enhanced after treatment with aggregated peptides and strongly inhibited after soluble A (42) treatment. Our data might provide insights into selective effects of specific forms of A (42)

show abstract

“…Thus, MAO-A is selectively inhibited by clorgyline and preferentially metabolizes serotonin: whereas MAO-B is inhibited by L-deprenyl and preferentially metabolizes benzylamine and phenylethylamine as substrates [4]. Among selective MAO inhibitors, those against MAO-A are used as anti-depressant and anti-anxiety drugs and have been claimed to protect neuronal cells against apoptosis [5,6]. In contrast, MAO-B inhibitors have been found to be beneficial in the treatment of Parkinson's disease and Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Preliminary Biological Evaluation of 1,3,5-Triazine Amino Acid Derivatives to Study Their MAO Inhibitors

et al. 2015

View full text Add to dashboard Cite

Three series of 4,6-dimethoxy-, 4,6-dipiperidino-and 4,6-dimorpholino-1,3,5-triazin-2-yl) amino acid derivatives were synthesized and characterized. A preliminary study for their monoamine oxidase inhibitory activity showed that compounds 7, 18, and 25 had MAO-A inhibition activity comparable to that of the standard clorgyline, with apparently more selective inhibitory activity toward MAO-A than MAO-B and no significant acute toxicity.

show abstract

Monoamine Oxidase-B Inhibition in Alzheimer's Disease

Cited by 233 publications

References 85 publications

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

Different effects of soluble and aggregated amyloid β42 on gene/protein expression and enzyme activity involved in insulin and APP pathways

Synthesis and Preliminary Biological Evaluation of 1,3,5-Triazine Amino Acid Derivatives to Study Their MAO Inhibitors

Contact Info

Product

Resources

About