Gaber El-Saber Batiha’s research while affiliated with Damanhour University and other places

Our study examines the potential of flavonoid-rich extracts from avocado seeds (Persea americana) in combating Alzheimer’s disease and diabetes. The antidiabetic activity of the extracts was assessed via the inhibition of α-amylase and α-glucosidase enzymes. Additionally, their anti-Alzheimer properties were evaluated through their anti-cholinesterase activities against AChE, BChE, and monoamine oxidase (MAO). Molecular docking and dynamics simulations were conducted to identify potential flavonoid inhibitors for the enzymes α-amylase, α-glucosidase, AChE, BChE, and monoamine oxidase. Notably, the extracts exhibited significant inhibitory activity against AChE (IC50 = 38.105 ± 0.32 µg/mL) and BChE (IC50 = 72.542 ± 1.470 µg/mL). MAO suppression protected against Fe2 + -mediated brain damage. Additionally, the flavonoid-rich extract of P. americana showed considerable inhibitory activity against α-amylase (IC50 = 608.516 ± 26.917 μg/mL) and α-glucosidase (IC50 = 790.570 ± 6.846 μg/mL) activities. HPLC–DAD profiling revealed the presence of gallic acid, caffeic acid, ferulic acid, rutin, p-coumaric acid, and quercetin. Molecular docking studies identified rutin, ferulic acid, and quercetin as the most promising ligands for the five protein targets investigated. Molecular simulations confirmed the stability of the protein‒ligand complexes, as evidenced by favorable thermodynamic parameters. Overall, our findings revealed that P. americana seed extracts have promising anti-Alzheimer’s and antidiabetic effects.

Alzheimer disease (AD) is a progressive neurodegenerative disease of the brain due to extracellular accumulation of Aβ. In addition, intracellular accumulation of hyperphosphorlyated tau protein which form neurofibrillary tangle (NFT) is associated with progressive neuronal injury and the development of AD. Aβ and NFTs interact together to induce inflammation and oxidative stress which further induce neurodegeneration in AD. The exact relationship between Aβ and tau, the two proteins that accumulate within these lesions, has proven elusive. A growing body of work supports the notion that Aβ may directly or indirectly interact with tau to accelerate NFTs formation. Aβ can adversely affect distinct molecular and cellular pathways, thereby facilitating tau phosphorylation, aggregation, mislocalization, and accumulation. Aβ may drive tau pathology by activating specific kinases, providing a straightforward mechanism by which Aβ may enhance tau hyperphosphorylation and NFT formation. Many cellular signaling pathways such as protein phosphatase 2A (PP2A), glycogen synthase kinase 3β (GSK3β), and phosphatase and tensin homologue (PTEN) are intricate in AD neuropathology. PP2A which involved in the dephosphorylation of tau protein is deregulated in AD, and correlated with cognitive impairment. PTEN is a critical regulator of neuronal growth, survival, and development, improving synaptic plasticity and axonal regeneration. Nevertheless, mutated PTEN is associated with the development of cognitive impairment by inhibiting the expression and the activity of PP2A. Furthermore, dysregulation of GSK3β affects Aβ, tau protein phosphorylation, synaptic plasticity and other signaling pathways involved in the pathogenesis of AD. Therefore, there is a close interaction among GSK3β, PTEN, and PP2A. GSK3β exaggerates AD neuropathology by inhibiting PP2A and activates the expression of PTEN. These findings specified a related interaction among GSK3β, PTEN, and PP2A, and modulation of the single component of this axis may not produce an effective effect against AD neuropathology. Modulation of this axis by metformin and statins can reduce AD neuropathology. Therefore, this review aims to discuss the role of GSK3β/PTEN/PP2A axis in AD neuropathology and how targeting of this axis by metformin and statins can produce effective therapeutic strategy in the management of AD. In conclusion, inhibition of GSK3β and PTEN and activation of PP2A may be more suitable than modulation of single signaling pathway. Metformin and statins by activating PP2A and inhibiting of GSK3β and PTEN attenuate the development and progression of AD. Graphical Abstract

Alzheimer disease (AD) is the main cause of dementia worldwide. AD is a progressive brain neurodegenerative disease due to genetic and environmental factors that induce a progressive accumulation of intracellular hyperphosphorylated tau protein and extracellular amyloid protein (Aβ). However, anti‐AD medications cannot reverse the fundamental AD neuropathology due to amyloid plaques and related oxidative stress and inflammatory reactions. Thus, targeting other pathways might be reasonable in the management of AD particular in alleviation of AD neuropathology and related reactions. Serotonin (5HT) neurotransmitter plays a crucial role in preventing neurodegeneration and related oxidative stress and inflammatory reactions. In addition, serotonergic system is highly dysregulated in many neurodegenerative diseases including AD. Deregulation of serotonin synthesis and its receptors are involved in the pathogenesis of AD . Therefore, this review we shall discuss how serotonergic system is affected in AD, and how 5HT modulators can reverse AD neuropathology and alleviate the associated neuropsychiatric disorders in AD patients.

Multiple sclerosis (MS) is a progressive demyelinating disease of the CNS, characterized by inflammation, the formation of CNS plaques, and damage to the neuronal myelin sheath (Graphical abstract). Fibroblast growth factor 21 (FGF21) is involved in various metabolic disorders and neurodegenerative diseases. FGF21 and its co‐receptor β‐Kloth are essential in the remyelination process of MS. Metformin, an insulin‐sensitizing drug that is the first‐line treatment for type 2 diabetes mellitus (T2DM), may have a potential neuroprotective impact by up‐regulating the production of FGF21, which may prevent the onset of neurodegenerative diseases including MS. The purpose of this review is to clarify how metformin affects MS neuropathology mechanistically via modifying FGF21. Metformin increases the expression of FGF21. Metformin also increases the expression of β‐Klotho, modulates oxidative stress, reduces glutamate‐induced excitotoxicity, and regulates platelet function and coagulation cascades. In conclusion, metformin can enhance the functional activity of FGF21 in counteracting the development and progression of MS. Preclinical and clinical studies are warranted in this regard.