2. Academic Validation
  3. Carnosic Acid Attenuates AβOs-Induced Apoptosis and Synaptic Impairment via Regulating NMDAR2B and Its Downstream Cascades in SH-SY5Y Cells

Carnosic Acid Attenuates AβOs-Induced Apoptosis and Synaptic Impairment via Regulating NMDAR2B and Its Downstream Cascades in SH-SY5Y Cells

  • Mol Neurobiol. 2022 Oct 13. doi: 10.1007/s12035-022-03032-w.
Wen-Ying Liu 1,  Yan Li 1,  Yan Li 1 2 3 4 5,  Ling-Zhi Xu 1 2 3 4 5,  Jian-Ping Jia 6 7 8 9 10
Affiliations

Affiliations

  • 1 Innovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, People's Republic of China.
  • 2 Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, People's Republic of China.
  • 3 Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, People's Republic of China.
  • 4 Center of Alzheimer's Disease, Collaborative Innovation Center for Brain Disorders, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, People's Republic of China.
  • 5 Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, 100053, People's Republic of China.
  • 6 Innovation Center for Neurological Disorders and Department of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Xicheng District, Beijing, People's Republic of China. [email protected].
  • 7 Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, People's Republic of China. [email protected].
  • 8 Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, People's Republic of China. [email protected].
  • 9 Center of Alzheimer's Disease, Collaborative Innovation Center for Brain Disorders, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, People's Republic of China. [email protected].
  • 10 Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, 100053, People's Republic of China. [email protected].
PMID: 36224322 DOI: 10.1007/s12035-022-03032-w
Abstract

Neuronal death and synaptic loss are principal pathological features of Alzheimer's disease (AD). Amyloid beta oligomers (AβOs) constitute the main neurotoxin underscoring AD pathology. AβOs interact with N-methyl-D-aspartate receptors (NMDARs), resulting in neurotoxic events, including activation of Apoptosis and synaptic impairment. Carnosic acid (CA), extracted from Salvia rosmarinus, has been verified its neuroprotective effects in AD. However, the precise mechanisms by which CA induces synaptic protection remain unclear. In this study, we established an in vitro AD model using SH-SY5Y human neuroblastoma cells. We observed that CA improved neuronal survival by suppressing Apoptosis. Moreover, CA restored synaptic impairments by increasing expression levels of brain-derived neurotrophic factor (BDNF), postsynaptic density protein-95 (PSD-95), and synaptophysin (Syn). Furthermore, we found these protective effects were dependent on inhibiting the phosphorylation of NMDAR subtype 2B (NMDAR2B), which further suppressed calcium overload and promoted activation of the extracellular signal-regulated kinase (ERK)-cAMP response element-binding protein (CREB) pathway. Administration of N-methyl-D-aspartic acid (NMDA), an agonist of NMDARs, abolished these effects of CA. Our findings demonstrate that CA exerts neuroprotective effects in an in vitro model of AD by regulating NMDAR2B and its downstream cascades, highlighting the therapeutic potential of CA as a NMDARs-targeted candidate in the treatment of AD.

Keywords

Alzheimer’s disease; Apoptosis; Carnosic acid; N-methyl-D-aspartate receptors; Salvia rosmarinus.

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