Navigating the Maze of Alzheimer’s disease by exploring BACE1: Discovery, current scenario, and future prospects

Iram, Faiza; Shahid, Mohammad; Ansari, Jaoud; Ashraf, Ghulam Md; Hassan, Md. Imtaiyaz; Islam, Asimul

doi:10.1016/j.arr.2024.102342

Ageing Research Reviews

2024

DOI: 10.1016/j.arr.2024.102342

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Navigating the Maze of Alzheimer’s disease by exploring BACE1: Discovery, current scenario, and future prospects

Faiza Iram,

Mohammad Shahid,

Jaoud Ansari

et al.

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Cited by 3 publications

References 165 publications

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Shahid

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Ageing Research Reviews

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Targeting tau in Alzheimer’s and beyond: Insights into pathology and therapeutic strategies

Singh,

Khan,

Shahid

et al. 2025

Ageing Research Reviews

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Ultrasensitive miRNA-135a-5p Biochip for Early Alzheimer's Disease Detection Utilizing Magneto-Optical Faraday Effect and Magnetoplasmonic Nanoparticles

Lin,

Huang,

Lin

et al. 2024

Sensors and Actuators B: Chemical

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Inhibitory Effects of Gliadin Hydrolysates on BACE1 Expression and APP Processing to Prevent Aβ Aggregation

Lin,

Hsieh,

Lai

et al. 2024

IJMS

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Alzheimer’s disease (AD), a leading neurodegenerative disorder, is closely associated with the accumulation of amyloid-beta (Aβ) peptides in the brain. The enzyme β-secretase (BACE1), pivotal in Aβ production, represents a promising therapeutic target for AD. While bioactive peptides derived from food protein hydrolysates have neuroprotective properties, their inhibitory effects on BACE1 remain largely unexplored. In this study, we evaluated the inhibitory potential of protein hydrolysates from gliadin, whey, and casein proteins prepared using bromelain, papain, and thermolysin. Through in vitro and cellular assays, bromelain-hydrolyzed gliadin (G-Bro) emerged as the most potent BACE1 inhibitor, with an IC50 of 0.408 mg/mL. G-Bro significantly reduced BACE1 expression and amyloid precursor protein (APP) processing in N2a/PS/APP cell cultures, suggesting its potential to attenuate Aβ aggregation. The unique peptide profile of G-Bro likely contributes to its inhibitory effect, with proline residues disrupting β-sheets, lysine residues introducing positive charges that hinder aggregation, hydrophobic residues stabilizing binding interactions, and glutamine residues enhancing solubility and stability. These findings highlight gliadin hydrolysates, particularly G-Bro, as potential natural BACE1 inhibitors with applications in dietary interventions for AD prevention. However, further studies are warranted to elucidate specific peptide interactions and their bioactivity in neural pathways to better understand their therapeutic potential.

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Navigating the Maze of Alzheimer’s disease by exploring BACE1: Discovery, current scenario, and future prospects

Cited by 3 publications

References 165 publications

Targeting tau in Alzheimer’s and beyond: Insights into pathology and therapeutic strategies

Targeting tau in Alzheimer’s and beyond: Insights into pathology and therapeutic strategies

Ultrasensitive miRNA-135a-5p Biochip for Early Alzheimer's Disease Detection Utilizing Magneto-Optical Faraday Effect and Magnetoplasmonic Nanoparticles

Inhibitory Effects of Gliadin Hydrolysates on BACE1 Expression and APP Processing to Prevent Aβ Aggregation

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