Molecular docking analysis of hyperphosphorylated tau protein with compounds derived from Bacopa monnieri and Withania somnifera

Abstract

Tau protein, the major player in Alzheimer disease forms neurofibrillary tangles in elderly people. Bramhi (Baccopa Monniera) is often used as an ayurvedic treatment for Alzheimer disease. Therefore it is of interest to study the interaction of compounds derived from Baccopa with the Tau protein involved in tangle formation. We show that compounds such as bacopaside II, bacopaside XII, and nicotine showed optimal binding features with the R2 repeat domain of hyperphosphorylated tau protein for further consideration in the context of Alzheimer disease (AD).

Amelioration of Amyloid‐β Induced Alzheimer's Disease by Bacopa monnieri through Modulation of Mitochondrial Dysfunction and GSK‐3β/Wnt/β‐Catenin Signaling

“…Moreover, as BM reduced the effect of aggregated Aβ 42 and its expression, which is supposedly involved in increased tau expression and hyperphosphorylation, can be a prominent factor in reducing tau‐related pathology Interestingly, a previous study on molecular docking analysis of BM constituents bacopaside II and bacopaside XII showed binding affinity to the hyperphosphorylated R2 domain of MAPT, inhibiting its aggregation that further validates its therapeutic potential. [ 64 ]…”

“…Moreover, as BM reduced the effect of aggregated A𝛽 42 and its expression, which is supposedly involved in increased tau expression and hyperphosphorylation, can be a prominent factor in reducing tau-related pathology Interestingly, a previous study on molecular docking analysis of BM constituents bacopaside II and bacopaside XII showed binding affinity to the hyperphosphorylated R2 domain of MAPT, inhibiting its aggregation that further validates its therapeutic potential. [64] Although, the neuroprotective and anti-amyloid effects of BM have been extensively demonstrated in various models of AD, the exact underlying molecular mechanism remains elusive. Based on the ability of BM extract to restrict tau hyperphosphorylation, in silico analysis was performed to determine the binding interactions between the BM constituents (Figure 6a) and the serine/threonine kinase GSK-3𝛽 (Figure 6b) and found that three components, bacopasaponin C (Figure 6c), bacopaside A (Figure 6d), and bacopaside I (Figure 6e) bind between Nterminal 𝛽-sheets and C-terminal helical region of GSK-3𝛽, mentioned in Table 1.…”

Amelioration of Amyloid‐β Induced Alzheimer's Disease by Bacopa monnieri through Modulation of Mitochondrial Dysfunction and GSK‐3β/Wnt/β‐Catenin Signaling

“…Moreover, as BM reduced the effect of aggregated Aβ 42 and its expression, which is supposedly involved in increased tau expression and hyperphosphorylation, can be a prominent factor in reducing tau‐related pathology Interestingly, a previous study on molecular docking analysis of BM constituents bacopaside II and bacopaside XII showed binding affinity to the hyperphosphorylated R2 domain of MAPT, inhibiting its aggregation that further validates its therapeutic potential. [ 64 ]…”

“…Moreover, as BM reduced the effect of aggregated A𝛽 42 and its expression, which is supposedly involved in increased tau expression and hyperphosphorylation, can be a prominent factor in reducing tau-related pathology Interestingly, a previous study on molecular docking analysis of BM constituents bacopaside II and bacopaside XII showed binding affinity to the hyperphosphorylated R2 domain of MAPT, inhibiting its aggregation that further validates its therapeutic potential. [64] Although, the neuroprotective and anti-amyloid effects of BM have been extensively demonstrated in various models of AD, the exact underlying molecular mechanism remains elusive. Based on the ability of BM extract to restrict tau hyperphosphorylation, in silico analysis was performed to determine the binding interactions between the BM constituents (Figure 6a) and the serine/threonine kinase GSK-3𝛽 (Figure 6b) and found that three components, bacopasaponin C (Figure 6c), bacopaside A (Figure 6d), and bacopaside I (Figure 6e) bind between Nterminal 𝛽-sheets and C-terminal helical region of GSK-3𝛽, mentioned in Table 1.…”

The Role of Bacopa monnieri in Alzheimer’s Disease: Mechanisms and Potential Clinical Use—A Review

“…Some in silico research suggests that brahmi’s active compounds may have an affinity for hyperphosphorylated tau protein and could prevent its tangle formation [ 43 ]. However, both the composition and the entire bioprocess of cultivating the plants and extracting active compounds are essential to the extract’s effectiveness as an anti-AD agent [ 44 ].…”

“…Inhibition occurs by interacting with the R2 repeat domain of the hyperphosphorylated protein. [43] Aβ aggregation ↓ The binding of bacoside A to amyloid oligomers prevents it from aggregating. [45][46][47] Neuroinflammation ↓ Decrease in TNF-α and IL-6 levels.…”

Amelioration of Amyloid‐β Induced Alzheimer's Disease by Bacopa monnieri through Modulation of Mitochondrial Dysfunction and GSK‐3β/Wnt/β‐Catenin Signaling

“…Moreover, as BM reduced the effect of aggregated Aβ 42 and its expression, which is supposedly involved in increased tau expression and hyperphosphorylation, can be a prominent factor in reducing tau‐related pathology Interestingly, a previous study on molecular docking analysis of BM constituents bacopaside II and bacopaside XII showed binding affinity to the hyperphosphorylated R2 domain of MAPT, inhibiting its aggregation that further validates its therapeutic potential. [ 64 ]…”

“…Moreover, as BM reduced the effect of aggregated A𝛽 42 and its expression, which is supposedly involved in increased tau expression and hyperphosphorylation, can be a prominent factor in reducing tau-related pathology Interestingly, a previous study on molecular docking analysis of BM constituents bacopaside II and bacopaside XII showed binding affinity to the hyperphosphorylated R2 domain of MAPT, inhibiting its aggregation that further validates its therapeutic potential. [64] Although, the neuroprotective and anti-amyloid effects of BM have been extensively demonstrated in various models of AD, the exact underlying molecular mechanism remains elusive. Based on the ability of BM extract to restrict tau hyperphosphorylation, in silico analysis was performed to determine the binding interactions between the BM constituents (Figure 6a) and the serine/threonine kinase GSK-3𝛽 (Figure 6b) and found that three components, bacopasaponin C (Figure 6c), bacopaside A (Figure 6d), and bacopaside I (Figure 6e) bind between Nterminal 𝛽-sheets and C-terminal helical region of GSK-3𝛽, mentioned in Table 1.…”

The Role of Bacopa monnieri in Alzheimer’s Disease: Mechanisms and Potential Clinical Use—A Review

“…Some in silico research suggests that brahmi’s active compounds may have an affinity for hyperphosphorylated tau protein and could prevent its tangle formation [ 43 ]. However, both the composition and the entire bioprocess of cultivating the plants and extracting active compounds are essential to the extract’s effectiveness as an anti-AD agent [ 44 ].…”

“…Inhibition occurs by interacting with the R2 repeat domain of the hyperphosphorylated protein. [43] Aβ aggregation ↓ The binding of bacoside A to amyloid oligomers prevents it from aggregating. [45][46][47] Neuroinflammation ↓ Decrease in TNF-α and IL-6 levels.…”

Amelioration of Amyloid‐β Induced Alzheimer's Disease by Bacopa monnieri through Modulation of Mitochondrial Dysfunction and GSK‐3β/Wnt/β‐Catenin Signaling

“…Moreover, as BM reduced the effect of aggregated Aβ 42 and its expression, which is supposedly involved in increased tau expression and hyperphosphorylation, can be a prominent factor in reducing tau‐related pathology Interestingly, a previous study on molecular docking analysis of BM constituents bacopaside II and bacopaside XII showed binding affinity to the hyperphosphorylated R2 domain of MAPT, inhibiting its aggregation that further validates its therapeutic potential. [ 64 ]…”

“…Moreover, as BM reduced the effect of aggregated A𝛽 42 and its expression, which is supposedly involved in increased tau expression and hyperphosphorylation, can be a prominent factor in reducing tau-related pathology Interestingly, a previous study on molecular docking analysis of BM constituents bacopaside II and bacopaside XII showed binding affinity to the hyperphosphorylated R2 domain of MAPT, inhibiting its aggregation that further validates its therapeutic potential. [64] Although, the neuroprotective and anti-amyloid effects of BM have been extensively demonstrated in various models of AD, the exact underlying molecular mechanism remains elusive. Based on the ability of BM extract to restrict tau hyperphosphorylation, in silico analysis was performed to determine the binding interactions between the BM constituents (Figure 6a) and the serine/threonine kinase GSK-3𝛽 (Figure 6b) and found that three components, bacopasaponin C (Figure 6c), bacopaside A (Figure 6d), and bacopaside I (Figure 6e) bind between Nterminal 𝛽-sheets and C-terminal helical region of GSK-3𝛽, mentioned in Table 1.…”

The Role of Bacopa monnieri in Alzheimer’s Disease: Mechanisms and Potential Clinical Use—A Review

“…Some in silico research suggests that brahmi’s active compounds may have an affinity for hyperphosphorylated tau protein and could prevent its tangle formation [ 43 ]. However, both the composition and the entire bioprocess of cultivating the plants and extracting active compounds are essential to the extract’s effectiveness as an anti-AD agent [ 44 ].…”

“…Inhibition occurs by interacting with the R2 repeat domain of the hyperphosphorylated protein. [43] Aβ aggregation ↓ The binding of bacoside A to amyloid oligomers prevents it from aggregating. [45][46][47] Neuroinflammation ↓ Decrease in TNF-α and IL-6 levels.…”