Molecular Mechanisms of Alzheimer’s Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy
Amyloid-β peptide (Aβ) is a critical cause of Alzheimer’s disease (AD). It is generated from amyloid precursor protein (APP) through cleavages by β-secretase and γ-secretase. γ-Secretase, which includes presenilin, is regulated by several stimuli. Tau protein has also been identified as a significan...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/2/89 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588840465858560 |
|---|---|
| author | Eun Hee Ahn Jae-Bong Park |
| author_facet | Eun Hee Ahn Jae-Bong Park |
| author_sort | Eun Hee Ahn |
| collection | DOAJ |
| description | Amyloid-β peptide (Aβ) is a critical cause of Alzheimer’s disease (AD). It is generated from amyloid precursor protein (APP) through cleavages by β-secretase and γ-secretase. γ-Secretase, which includes presenilin, is regulated by several stimuli. Tau protein has also been identified as a significant factor in AD. In particular, Tau phosphorylation is crucial for neuronal impairment, as phosphorylated Tau detaches from microtubules, leading to the formation of neurofibrillary tangles and the destabilization of the microtubule structure. This instability in microtubules damages axons and dendrites, resulting in neuronal impairment. Notably, Aβ is linked to Tau phosphorylation. Another crucial factor in AD is neuroinflammation, primarily occurring in the microglia. Microglia possess several receptors that bind with Aβ, triggering the expression and release of an inflammatory factor, although their main physiological function is to phagocytose debris and pathogens in the brain. NF-κB activation plays a major role in neuroinflammation. Additionally, the production of reactive oxygen species (ROS) in the microglia contributes to this neuroinflammation. In microglia, superoxide is produced through NADPH oxidase, specifically NOX2. Rho GTPases play an essential role in regulating various cellular processes, including cytoskeletal rearrangement, morphology changes, migration, and transcription. The typical function of Rho GTPases involves regulating actin filament formation. Neurons, with their complex processes and synapse connections, rely on cytoskeletal dynamics for structural support. Other brain cells, such as astrocytes, microglia, and oligodendrocytes, also depend on specific cytoskeletal structures to maintain their unique cellular architectures. Thus, the aberrant regulation of Rho GTPases activity can disrupt actin filaments, leading to altered cell morphology, including changes in neuronal processes and synapses, and potentially contributing to brain diseases such as AD. |
| format | Article |
| id | doaj-art-67e51f8647a84cdf8c27961e381910e2 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-67e51f8647a84cdf8c27961e381910e22025-01-24T13:26:38ZengMDPI AGCells2073-44092025-01-011428910.3390/cells14020089Molecular Mechanisms of Alzheimer’s Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal TherapyEun Hee Ahn0Jae-Bong Park1Department of Physiology, Hallym University College of Medicine, Chuncheon 24252, Kangwon-do, Republic of KoreaDepartment of Biochemistry, Hallym University College of Medicine, Chuncheon 24252, Kangwon-do, Republic of KoreaAmyloid-β peptide (Aβ) is a critical cause of Alzheimer’s disease (AD). It is generated from amyloid precursor protein (APP) through cleavages by β-secretase and γ-secretase. γ-Secretase, which includes presenilin, is regulated by several stimuli. Tau protein has also been identified as a significant factor in AD. In particular, Tau phosphorylation is crucial for neuronal impairment, as phosphorylated Tau detaches from microtubules, leading to the formation of neurofibrillary tangles and the destabilization of the microtubule structure. This instability in microtubules damages axons and dendrites, resulting in neuronal impairment. Notably, Aβ is linked to Tau phosphorylation. Another crucial factor in AD is neuroinflammation, primarily occurring in the microglia. Microglia possess several receptors that bind with Aβ, triggering the expression and release of an inflammatory factor, although their main physiological function is to phagocytose debris and pathogens in the brain. NF-κB activation plays a major role in neuroinflammation. Additionally, the production of reactive oxygen species (ROS) in the microglia contributes to this neuroinflammation. In microglia, superoxide is produced through NADPH oxidase, specifically NOX2. Rho GTPases play an essential role in regulating various cellular processes, including cytoskeletal rearrangement, morphology changes, migration, and transcription. The typical function of Rho GTPases involves regulating actin filament formation. Neurons, with their complex processes and synapse connections, rely on cytoskeletal dynamics for structural support. Other brain cells, such as astrocytes, microglia, and oligodendrocytes, also depend on specific cytoskeletal structures to maintain their unique cellular architectures. Thus, the aberrant regulation of Rho GTPases activity can disrupt actin filaments, leading to altered cell morphology, including changes in neuronal processes and synapses, and potentially contributing to brain diseases such as AD.https://www.mdpi.com/2073-4409/14/2/89Alzheimer’s diseaseamyloid-betatau phosphorylationneuroinflammationRhoA GTPase |
| spellingShingle | Eun Hee Ahn Jae-Bong Park Molecular Mechanisms of Alzheimer’s Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy Cells Alzheimer’s disease amyloid-beta tau phosphorylation neuroinflammation RhoA GTPase |
| title | Molecular Mechanisms of Alzheimer’s Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy |
| title_full | Molecular Mechanisms of Alzheimer’s Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy |
| title_fullStr | Molecular Mechanisms of Alzheimer’s Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy |
| title_full_unstemmed | Molecular Mechanisms of Alzheimer’s Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy |
| title_short | Molecular Mechanisms of Alzheimer’s Disease Induced by Amyloid-β and Tau Phosphorylation Along with RhoA Activity: Perspective of RhoA/Rho-Associated Protein Kinase Inhibitors for Neuronal Therapy |
| title_sort | molecular mechanisms of alzheimer s disease induced by amyloid β and tau phosphorylation along with rhoa activity perspective of rhoa rho associated protein kinase inhibitors for neuronal therapy |
| topic | Alzheimer’s disease amyloid-beta tau phosphorylation neuroinflammation RhoA GTPase |
| url | https://www.mdpi.com/2073-4409/14/2/89 |
| work_keys_str_mv | AT eunheeahn molecularmechanismsofalzheimersdiseaseinducedbyamyloidbandtauphosphorylationalongwithrhoaactivityperspectiveofrhoarhoassociatedproteinkinaseinhibitorsforneuronaltherapy AT jaebongpark molecularmechanismsofalzheimersdiseaseinducedbyamyloidbandtauphosphorylationalongwithrhoaactivityperspectiveofrhoarhoassociatedproteinkinaseinhibitorsforneuronaltherapy |