Therapeutic potential of neurotrophic factors in Alzheimer’s Disease

Nasrolahi, Ava; Javaherforooshzadeh, Fatemeh; Jafarzadehgharehziaaddin, Mohsen; Mahmoudi, Javad; Asl, Khadijeh Dizaji; Shabani, Zahra

doi:10.1007/s11033-021-06968-9

Cited by 21 publications

(16 citation statements)

References 104 publications

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“…Improving or reversing neurotrophic factor deficiency is being considered as potentially viable options for a wide range of neurological conditions including brain injury, AD and Parkinson's disease [116][117][118][119][120][121]. The results of this study provide exciting new knowledge that GlyNAC supplementation can successfully improve and reverse the deficient protein expression of BDNF, GDNF and NGF in the aging brain and thereby play a key role in maintaining and promoting brain health in aging.…”

Section: Glynac Supplementation Improves Neurotrophic Factors In the ...mentioning

confidence: 88%

GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Old Mice Improves Brain Glutathione Deficiency, Oxidative Stress, Glucose Uptake, Mitochondrial Dysfunction, Genomic Damage, Inflammation and Neurotrophic Factors to Reverse Age-Associated Cognitive Decline: Implications for Improving Brain Health in Aging

2023

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Cognitive decline frequently occurs with increasing age, but mechanisms contributing to age-associated cognitive decline (ACD) are not well understood and solutions are lacking. Understanding and reversing mechanisms contributing to ACD are important because increased age is identified as the single most important risk factor for dementia. We reported earlier that ACD in older humans is associated with glutathione (GSH) deficiency, oxidative stress (OxS), mitochondrial dysfunction, glucose dysmetabolism and inflammation, and that supplementing GlyNAC (glycine and N-acetylcysteine) improved these defects. To test whether these defects occur in the brain in association with ACD, and could be improved/reversed with GlyNAC supplementation, we studied young (20-week) and old (90-week) C57BL/6J mice. Old mice received either regular or GlyNAC supplemented diets for 8 weeks, while young mice received the regular diet. Cognition and brain outcomes (GSH, OxS, mitochondrial energetics, autophagy/mitophagy, glucose transporters, inflammation, genomic damage and neurotrophic factors) were measured. Compared to young mice, the old-control mice had significant cognitive impairment and multiple brain defects. GlyNAC supplementation improved/corrected the brain defects and reversed ACD. This study finds that naturally-occurring ACD is associated with multiple abnormalities in the brain, and provides proof-of-concept that GlyNAC supplementation corrects these defects and improves cognitive function in aging.

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Section: Glynac Supplementation Improves Neurotrophic Factors In the ...mentioning

confidence: 88%

GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Old Mice Improves Brain Glutathione Deficiency, Oxidative Stress, Glucose Uptake, Mitochondrial Dysfunction, Genomic Damage, Inflammation and Neurotrophic Factors to Reverse Age-Associated Cognitive Decline: Implications for Improving Brain Health in Aging

2023

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“…Neurotrophic factors are neuroprotective, encouraging axon regeneration and improving neuronal cell function [13]. Because of their promising outcomes in other neurodegenerative disorders of the central nervous system [14][15][16], NTFs are an appealing therapeutic target to explore in glaucoma.…”

Section: Neurotrophic Factorsmentioning

confidence: 99%

Neuroprotection in Glaucoma: Basic Aspects and Clinical Relevance

Kuo

Liu

2022

JPM

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Glaucoma is a neurodegenerative disease that affects primarily the retinal ganglion cells (RGCs). Increased intraocular pressure (IOP) is one of the major risk factors for glaucoma. The mainstay of current glaucoma therapy is limited to lowering IOP; however, controlling IOP in certain patients can be futile in slowing disease progression. The understanding of potential biomolecular processes that occur in glaucomatous degeneration allows for the development of glaucoma treatments that modulate the death of RGCs. Neuroprotection is the modification of RGCs and the microenvironment of neurons to promote neuron survival and function. Numerous studies have revealed effective neuroprotection modalities in animal models of glaucoma; nevertheless, clinical translation remains a major challenge. In this review, we select the most clinically relevant treatment strategies, summarize preclinical and clinical data as well as recent therapeutic advances in IOP-independent neuroprotection research, and discuss the feasibility and hurdles of each therapeutic approach based on possible pathogenic mechanisms. We also summarize the potential therapeutic mechanisms of various agents in neuroprotection related to glutamate excitotoxicity.

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“…The hypothesis of NTFs in AD supports the idea that AD is caused by a deficiency in neurotrophic pathways, making NTF targeting a potential therapeutic tool for AD. The anticipated roles of NTFs in AD treatment have been discussed recently by various labs [ 28 , 29 , 30 , 31 ]. Most NTFs exert their effects via signaling through specific transmembrane receptor tyrosine kinases (RTKs) and are typically classified into the following groups: (1) Neurotrophins, the most-studied family of NTFs.…”

Section: Ntfs and Admentioning

confidence: 99%

“…The neurotrophic factor hypothesis for AD pathogenesis supports the idea that targeting NTF signaling pathways is a potential therapeutic tool for AD. The anticipated roles of NTFs (typically NGF and BDNF) in AD treatment have been discussed recently by various labs [ 28 , 29 , 30 ]. Original research exploring the roles of NTFs on AD was initiated in NGF and has accordingly transitioned to clinical trials [ 68 , 69 ].…”

Section: Targeting the Common Pathway For Preventing Both Amyloidogen...mentioning

confidence: 99%

Amyloidogenesis and Neurotrophic Dysfunction in Alzheimer’s Disease: Do They have a Common Regulating Pathway?

Jiao

Jiang

et al. 2022

Cells

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The amyloid cascade hypothesis has predominately been used to describe the pathogenesis of Alzheimer’s disease (AD) for decades, as Aβ oligomers are thought to be the prime cause of AD. Meanwhile, the neurotrophic factor hypothesis has also been proposed for decades. Accumulating evidence states that the amyloidogenic process and neurotrophic dysfunction are mutually influenced and may coincidently cause the onset and progress of AD. Meanwhile, there are intracellular regulators participating both in the amyloidogenic process and neurotrophic pathways, which might be the common original causes of amyloidogenesis and neurotrophic dysfunction. In this review, the current understanding regarding the role of neurotrophic dysfunction and the amyloidogenic process in AD pathology is briefly summarized. The mutual influence of these two pathogenesis pathways and their potential common causal pathway are further discussed. Therapeutic strategies targeting the common pathways to simultaneously prevent amyloidogenesis and neurotrophic dysfunction might be anticipated for the disease-modifying treatment of AD.

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Therapeutic potential of neurotrophic factors in Alzheimer’s Disease

Cited by 21 publications

References 104 publications

Neuroprotection in Glaucoma: Basic Aspects and Clinical Relevance

Amyloidogenesis and Neurotrophic Dysfunction in Alzheimer’s Disease: Do They have a Common Regulating Pathway?

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