Phenylpropanoids and Alzheimer's disease: A potential therapeutic platform

Kolaj, Igri; Liyanage, S. Imindu; Weaver, Donald F.

doi:10.1016/j.neuint.2018.08.001

Cited by 29 publications

(20 citation statements)

References 196 publications

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“…AD is a neurodegenerative disease characterized by progressive dementia, neuroinflammation, intracellular neurofibrillary tangles and accumulation of extracellular plaques. There appear to be four main causes: the hypothesis of abnormal folding and aggregation of amyloid-beta/tau protein, activation of the innate immune system, mitochondrial dysfunction and oxidative stress [9]. In this study, we collected the gene expression profiles and normal control brain tissues of AD in GSE110226 from GEO.…”

Section: Discussionmentioning

confidence: 99%

Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer’s disease

Zou

Wang

Huang

et al. 2019

Aging

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease that ranks as the fourth most common cause of death in developed countries. In our study, genes differentially expressed between AD and healthy individuals were identified and used to construct protein-protein interaction (PPI) networks. The AD-related PPI network was used to identify functional modules, and enrichment analysis showed that they were significantly involved in “Alzheimer’s disease”, “apoptosis”, and related pathways. We predicted non-coding RNAs and transcription factors that may regulate the functional modules. The expression of hub genes and transcription factors was validated in an independent data set. The results in this study provide several candidates for further research on mechanisms of AD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer’s disease

Zou

Wang

Huang

et al. 2019

Aging

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“…In this heterogeneous group of substances, many subclasses have been identified such as stilbenoids, flavonoids, curcuminoids, phenolate esters, and lignans. These compounds showed an effect against the Aβ peptide and tau pathologies, on the activation of the inflammation response, on the oxidative stress, and also on the mitochondrial dysfunction (Kolaj et al, 2018). Between others, resveratrol , quercetin , wogonin , epigallocatechin-3-gallate ( EGCG ), and curcumin were already tested and showed to promote mitochondrial biogenesis, to impede apoptotic pathways through inhibition of DNA fragmentation, ROS formation, and caspase-3 activation, and to reduce perturbation of mtΔΨ and ATP levels (see also Table 1 for the effects of phenylpropanoids on mitochondria in AD models) (Lagouge et al, 2006; Davis et al, 2009; Im et al, 2012; Valenti et al, 2013; Reddy et al, 2016).…”

Section: Mitochondrial Therapies In Admentioning

confidence: 99%

Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update

2019

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Alzheimer disease (AD) is a progressive and deleterious neurodegenerative disorder that affects mostly the elderly population. At the moment, no effective treatments are available in the market, making the whole situation a compelling challenge for societies worldwide. Recently, novel mechanisms have been proposed to explain the etiology of this disease leading to the new concept that AD is a multifactor pathology. Among others, the function of mitochondria has been considered as one of the intracellular processes severely compromised in AD since the early stages and likely represents a common feature of many neurodegenerative diseases. Many mitochondrial parameters decline already during the aging, reaching an extensive functional failure concomitant with the onset of neurodegenerative conditions, although the exact timeline of these events is still unclear. Thereby, it is not surprising that mitochondria have been already considered as therapeutic targets in neurodegenerative diseases including AD. Together with an overview of the role of mitochondrial dysfunction, this review examines the pros and cons of the tested therapeutic approaches targeting mitochondria in the context of AD. Since mitochondrial therapies in AD have shown different degrees of progress, it is imperative to perform a detailed analysis of the significance of mitochondrial deterioration in AD and of a pharmacological treatment at this level. This step would be very important for the field, as an effective drug treatment in AD is still missing and new therapeutic concepts are urgently needed.

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“…Besides all the compounds listed until now, there are several other molecules which may act at the same time on many pathways linked to mitochondrial dysfunctions (for a general overview see Table 5). For example, phenylpropanoids are natural molecules derived from the amino acid l-phenylalanine; among them, resveratrol, curcumin, and flavonoids (including epigallocatechin-gallate, quercetin and wogonin) can (i) regulate mitochondrial biogenesis, enhancing the expression of several activators (i.e., PGC-1α, SIRT1, Nrf1, Nrf2, and TFAM), (ii) improve mitochondrial bioenergetics, (iii) enhance ATP production, and (iv) counteract apoptotic pathways (as described in Kolaj et al [212]). Furthermore, they are able to prevent oxidative stress (i) quenching free radicals through a direct mechanism [213], (ii) upregulating the expression of antioxidative enzymes via the activation of different signaling pathways (i.e., Nrf2), even increasing GSH production [214,215], and (iii) inhibiting ROS-forming enzymes like XO and NOX [216].…”

Section: Compounds Targeting Multiple Mitochondrial Dysfunctionsmentioning

confidence: 99%

Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

Stanga

Caretto

Boido

et al. 2020

IJMS

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Mitochondria play a central role in a plethora of processes related to the maintenance of cellular homeostasis and genomic integrity. They contribute to preserving the optimal functioning of cells and protecting them from potential DNA damage which could result in mutations and disease. However, perturbations of the system due to senescence or environmental factors induce alterations of the physiological balance and lead to the impairment of mitochondrial functions. After the description of the crucial roles of mitochondria for cell survival and activity, the core of this review focuses on the “mitochondrial switch” which occurs at the onset of neuronal degeneration. We dissect the pathways related to mitochondrial dysfunctions which are shared among the most frequent or disabling neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, Amyotrophic Lateral Sclerosis, and Spinal Muscular Atrophy. Can mitochondrial dysfunctions (affecting their morphology and activities) represent the early event eliciting the shift towards pathological neurobiological processes? Can mitochondria represent a common target against neurodegeneration? We also review here the drugs that target mitochondria in neurodegenerative diseases.

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Phenylpropanoids and Alzheimer's disease: A potential therapeutic platform

Cited by 29 publications

References 196 publications

Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer’s disease

Analysis of transcription factor- and ncRNA-mediated potential pathogenic gene modules in Alzheimer’s disease

Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update

Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

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