Bridging pathway dysfunction and therapy: novel compounds for neuroprotection
Shraddha Patel1, Chandrabhan Prajapati1, Sachchida Nand Rai2
1Centre of Experimental Medicine and Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005 India.
Abstract:
Recent finding in the field of neurodegenerative disease shows that dysregulation of signaling pathways like PI3K/AKT/mTOR, MAPK/ERK, NF-κB, Wnt/β-Catenin and apoptotic regulator, mitochondrial dysfunction, play pivotal role in the progression of Alzheimer, Parkinson, and other disease. Recent research indicates that disruptions in these interrelated pathways lead to oxidative harm, mitochondrial malfunction, aberrant protein aggregates, synaptic dysfunction, and eventually neuronal death. Numerous naturally occurring bioactive substances, like as genistein, curcumin, luteolin, and others, show great promise in combating these degenerative processes. These compounds improve neuronal survival as well as functional outcomes in laboratory experiments by modulating several signaling targets, restoring PI3K-Akt-mTOR, MAPK-ERK, Wnt/β-catenin, and NF-κB activity, restoring mitochondrial bioenergetics, limiting apoptosis, and reducing amyloid- β, α-synuclein accumulation. Numerous natural compounds with well-defined mechanisms of the actions and multitargeted therapeutic benefits are highlighted by a comprehensive evaluation of the available data, providing reliable and more affordable substitutes for one- target synthetic medicines. Despite its potential, issues including low bioavailability and low translational success persist. Overall, the results highlight the potential of understudied phytochemicals for creating more robust therapies against the development of neurodegenerative diseases and uncover important signaling centers that can be regulated by natural substances.
Insights
Natural compounds show promise for treating neurodegenerative diseases by targeting key signaling pathways like PI3K/AKT/mTOR and MAPK/ERK, offering potential alternatives to synthetic drugs.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Neurodegenerative diseases like Alzheimer's and Parkinson's involve dysregulated signaling pathways.
- Mitochondrial dysfunction, oxidative stress, and protein aggregation are key pathological features.
Purpose of the Study:
- To evaluate the potential of natural bioactive substances in combating neurodegenerative disease progression.
- To identify signaling pathways and molecular targets amenable to natural compound intervention.
Main Methods:
- Review of existing literature on signaling pathways (PI3K/AKT/mTOR, MAPK/ERK, NF-κB, Wnt/β-Catenin) in neurodegeneration.
- Analysis of studies on natural compounds (e.g., genistein, curcumin, luteolin) and their effects on these pathways.
- Assessment of evidence for neuroprotection, mitochondrial restoration, and reduction of protein aggregates.
Main Results:
- Natural compounds modulate key signaling pathways, improving neuronal survival and function.
- These substances restore mitochondrial bioenergetics, reduce apoptosis, and decrease pathological protein aggregates (amyloid-β, α-synuclein).
- Multitargeted natural compounds offer potential as affordable alternatives to single-target synthetic drugs.
Conclusions:
- Phytochemicals hold significant potential for developing novel therapies against neurodegenerative diseases.
- Targeting specific signaling centers with natural compounds presents a promising therapeutic strategy.
- Further research is needed to address challenges like bioavailability and translational success.
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