Prolong treatment with Trans-ferulic acid mitigates bioenergetics loss and restores mitochondrial dynamics in streptozotocin-induced sporadic dementia of Alzheimer's type

Zafeer, Mohd Faraz; Firdaus, Fakiha; Anis, Ehraz; Hossain, Mohammad Salim

doi:10.1016/j.neuro.2019.04.006

Cited by 38 publications

(24 citation statements)

References 63 publications

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“…Because upregulation of fission can lead to mitochondrial fragmentation and ROS exacerbation, and this oxidative stress can in turn cause mitochondrial fragmentation to form a vicious cycle (Ježek, Cooper, & Strich, ); the free radical quenching potential of FA might explain its ability to restore normal functioning in lesioned animals. In a previous study, we had observed that FA mitigated reduced expression of respiratory chain Complexes I–IV and reduced activity of Complex V, consequent reduced MMP and prolonged opening of mitochondrial permeability transition pore (mPTP) in an in vivo model of Alzheimer's disease (Zafeer, Firdaus, Anis, & Mobarak Hossain, ). Sudden changes in MMP increase susceptibility to prolonged mPTP opening, leading to further exacerbation of oxidative stress and advancement of apoptotic cascade.…”

Section: Discussionmentioning

confidence: 99%

Ferulic acid reinstates mitochondrial dynamics through PGC1α expression modulation in 6‐hydroxydopamine lesioned rats

Anis

Zafeer

Firdaus

et al. 2019

Phytotherapy Research

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Disruption of the tightly regulated mitochondrial dynamics and energy homeostasis leads to oxidative stress and apoptotic cell death, as observed in neurodegenerative disorders such as Parkinson's disease (PD). Polyphenolic plant derivatives have been shown to alleviate such pathological features and have been used in models of neurodegenerative disorders in previous reports. In the current study, we utilized a 6hydroxydopamine (6-OHDA) lesioned rat model of PD to explore the protective efficacy of polyphenolic phytochemical ferulic acid (FA) against mitochondrial dysfunction and explored its effect on gene and protein expression of mitochondrial dynamics regulators dynamin-related protein 1 (Drp1)/mitofusin 2 (Mfn2) in lesioned animals. We also evaluated its effect on expression of mitochondrial biogenesis regulator PGC1α and apoptotic regulators BAX, cyt c, p53, and cleaved PARP. We found that oral FA supplementation alleviated 6-OHDA induced oxidative stress, DNA fragmentation, morphological changes, and blocked apoptotic cascade. FA also reduced mitochondrial Drp1 expression and increased gene and protein expression of PGC1α, thereby regulating expression of its downstream target Mfn2 and restoring mitochondrial dynamics in lesioned animals. Our data suggest that targeting mitochondrial dynamics through modulation of PGC1α can prove to be a potent preventive strategy against PD pathology.

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Section: Discussionmentioning

confidence: 99%

Ferulic acid reinstates mitochondrial dynamics through PGC1α expression modulation in 6‐hydroxydopamine lesioned rats

Anis

Zafeer

Firdaus

et al. 2019

Phytotherapy Research

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“…Moreover, Zafeer et al [60] evaluated the effect of trans-ferulic acid (FA) on the intracerebral-ventricular streptozocin (ICV-STZ) rat model. They found an increase and decrease in mitochondrial Drp1 and Mfn2 protein levels, respectively.…”

Section: Mfn2 As a Potential Target In Alzheimer's Diseasementioning

confidence: 99%

Back to The Fusion: Mitofusin-2 in Alzheimer’s Disease

Sita

Hrelia

Graziosi

et al. 2020

JCM

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Mitochondria are dynamic organelles that undergo constant fission and fusion. Mitochondria dysfunction underlies several human disorders, including Alzheimer's disease (AD). Preservation of mitochondrial dynamics is fundamental for regulating the organelle's functions. Several proteins participate in the regulation of mitochondrial morphology and networks, and among these, Mitofusin 2 (Mfn2) has been extensively studied. This review focuses on the role of Mfn2 in mitochondrial dynamics and in the crosstalk between mitochondria and the endoplasmic reticulum, in particular in AD. Understanding how this protein may be related to AD pathogenesis will provide essential information for the development of therapies for diseases linked to disturbed mitochondrial dynamics, as in AD.

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“…For example, paeoniflorin contained in LSZ can significantly improve the performance of aged wild-type rats in passive avoidance tasks (Baltina et al, 2019). Ferulic acid was reported to improve the escape latency of normal mice (Zafeer et al, 2019). These studies imply that LSZ may protect normal cognition against the damages caused by AD.…”

Section: Discussionmentioning

confidence: 97%

LongShengZhi Capsule Attenuates Alzheimer-Like Pathology in APP/PS1 Double Transgenic Mice by Reducing Neuronal Oxidative Stress and Inflammation

Yin

Wang

Zheng

et al. 2020

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It may be caused by oxidative stress, inflammation, and cerebrovascular dysfunctions in the brain. LongShengZhi Capsule (LSZ), a traditional Chinese medicine, has been approved by the China Food and Drug Administration for treatment of patients with cardiovascular/cerebrovascular disease. LSZ contains several neuroprotective ingredients, including Hirudo, Astmgali Radix, Carthami Flos (Honghua), Persicae Semen (Taoren), Acori Tatarinowii Rhizoma (Shichangpu), and Acanthopanax Senticosus (Ciwujia). In this study, we aimed to determine the effect of LSZ on the AD process. Double transgenic mice expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1) to model AD were treated with LSZ for 7 months starting at 2 months of age. LSZ significantly improved the cognition of the mice without adverse effects, indicating its high degree of safety and efficacy after a long-term treatment. LSZ reduced AD biomarker Aβ plaque accumulation by inhibiting β-secretase and γ-secretase gene expression. LSZ also reduced p-Tau expression, cell death, and inflammation in the brain. Consistently, in vitro, LSZ ethanol extract enhanced neuronal viability by reducing L-glutamic acid-induced oxidative stress and inflammation in HT-22 cells. LSZ exerted antioxidative effects by enhancing superoxide dismutase and glutathione peroxidase expression, reduced Aβ accumulation by inhibiting β-secretase and γ-secretase mRNA expression, and decreased p-Tau level by inhibiting NF-κB-mediated inflammation. It also demonstrated neuroprotective effects by regulating the Fas cell surface death receptor/B-cell lymphoma 2/p53 pathway. Taken together, our study demonstrates the antioxidative stress, anti-inflammatory, and neuroprotective effects of LSZ in the AD-like pathological process and suggests it could be a potential medicine for AD treatment.

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Prolong treatment with Trans-ferulic acid mitigates bioenergetics loss and restores mitochondrial dynamics in streptozotocin-induced sporadic dementia of Alzheimer's type

Cited by 38 publications

References 63 publications

Ferulic acid reinstates mitochondrial dynamics through PGC1α expression modulation in 6‐hydroxydopamine lesioned rats

Ferulic acid reinstates mitochondrial dynamics through PGC1α expression modulation in 6‐hydroxydopamine lesioned rats

Back to The Fusion: Mitofusin-2 in Alzheimer’s Disease

LongShengZhi Capsule Attenuates Alzheimer-Like Pathology in APP/PS1 Double Transgenic Mice by Reducing Neuronal Oxidative Stress and Inflammation

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