Testing the potential of peptides as a treatment for autism
This study aims to investigate the efficacy of PEDF peptides as a medication for autism spectrum disorder and ADNP syndrome.
Pigment Epithelium-Derived Factor (PEDF) is localized at chromosome 17p13.3, and deletions or duplications of this chromosome region result in neurodevelopmental disorders, such as Miller-Dieker syndrome and 17p13.3 duplication syndrome, related to ASD. We recently have found that PEDF plays a critical role in neuronal morphogenesis and neural activity in vivo, including neurite formation, spine formation and calcium signaling. Studies have indicated the possibility of PEDF-derived peptide as a potential medication for tumors and retinopathy. However, little is known about PEDF functions in neurodevelopment in the cortex and the effects of the peptides in neurodevelopmental disorders, such as autism.
In addition, we are interested in testing the peptides in the ADNP syndrome, which is caused by a mutation in the ADNP (activity-dependent neuroprotective protein) gene and associated with a variety of symptoms, such as ASD, ADHD and intellectual disability.
Autism spectrum disorder (ASD) is characterized by four core symptoms, which are 1) impaired communication and social interaction, 2) restrictive interests, 3) repetitive behaviors, and 4) irritability. Many patients with autism spectrum disorder experience daily pain and frustration, as many cannot make friends, engage in social activities, or find comfort in most environments. ASD is a huge burden on not only patients but also their families and local and federal health systems. There is an urgent need to alleviate these burdens, but to date, no effective treatments addressing the cause of autism spectrum disorder exist. Current medications are limited only to reducing irritability. To relieve the severe burdens of this disease, developing improved and novel medications that can address the other core symptoms of ASD are essential.
Pigment Epithelium-Derived Factor (PEDF) is localized at chromosome 17p13.3, and deletions or duplications of this chromosome region result in neurodevelopmental disorders, such as Miller-Dieker syndrome and 17p13.3 duplication syndrome, related to ASD. We recently have found that PEDF plays a critical role in neuronal morphogenesis and neural activity in vivo, including neurite formation, spine formation and calcium signaling. Studies have indicated the possibility of PEDF-derived peptide as a potential medication for tumors and retinopathy. However, little is known about PEDF functions in neurodevelopment in the cortex and the effects of the peptides in neurodevelopmental disorders, such as autism.
In addition, we are interested in testing the peptides in the ADNP syndrome, which is caused by a mutation in the ADNP (activity-dependent neuroprotective protein) gene and associated with a variety of symptoms, such as ASD, ADHD and intellectual disability.
Autism spectrum disorder (ASD) is characterized by four core symptoms, which are 1) impaired communication and social interaction, 2) restrictive interests, 3) repetitive behaviors, and 4) irritability. Many patients with autism spectrum disorder experience daily pain and frustration, as many cannot make friends, engage in social activities, or find comfort in most environments. ASD is a huge burden on not only patients but also their families and local and federal health systems. There is an urgent need to alleviate these burdens, but to date, no effective treatments addressing the cause of autism spectrum disorder exist. Current medications are limited only to reducing irritability. To relieve the severe burdens of this disease, developing improved and novel medications that can address the other core symptoms of ASD are essential.
Etiology of the 17p13.3 Microdeletion (Miller-Dieker Syndrome) and Microduplication Syndrome Related to Autism
The aim of this project is to study the etiology of the 17p13.3 microdeletion (Miller-Dieker syndrome) and microduplication syndrome. We are interested in determining the functions of 26 genes involved in the 17p13.3 microdeletion (Miller-Dieker syndrome) and microduplication syndrome associated with autism.
In chromosome 17p13.3, there is a hotspot, called MDS critical region, which is often deleted or duplicated in MDS and the 17p13.3 duplication syndrome. there are 26 genes in MDS critical region, but the functions of many of those 26 genes in cortical development have not been clarified. Therefore, to understand the etiology of neurodevelopmental disorders, it is of importance to investigate the functions in neurodevelopment.
It is known that Lis1, Crk and 14-3-3epsilon in 17p13.3 are responsible genes for MDS. However, the MDS critical chromosome region contains 26 genes, including PEDF (Serpinf1). Thus, we know a bit about MDS etiology, but we still don't know many things about MDS.
In chromosome 17p13.3, there is a hotspot, called MDS critical region, which is often deleted or duplicated in MDS and the 17p13.3 duplication syndrome. there are 26 genes in MDS critical region, but the functions of many of those 26 genes in cortical development have not been clarified. Therefore, to understand the etiology of neurodevelopmental disorders, it is of importance to investigate the functions in neurodevelopment.
It is known that Lis1, Crk and 14-3-3epsilon in 17p13.3 are responsible genes for MDS. However, the MDS critical chromosome region contains 26 genes, including PEDF (Serpinf1). Thus, we know a bit about MDS etiology, but we still don't know many things about MDS.
Neuronal Morphogenesis in the Developing Cortex
This project aims to investigate the cellular and molecular mechanisms underlying neuronal morphogenesis, such as neurite formation, spine formation, and synaptogenesis, in the developing cerebral cortex.
Neuronal morphogenesis occurs relatively in early-stage of cortical development. The defects in these early steps largely affect the later steps, such as neural connection and activity. Recent studies using ASD animal models indicate the defects in neuronal morphogenesis, not only spine/synapse formation but also neurite formation. Thus, a more comprehensive understanding of neuronal morphogenesis is essential to understand the etiology of neurodevelopmental disorders.
Neurite formation is an early cellular event during cortical developments. The defects in this step affect many later steps, such as neural connectivity and activity. Therefore, the full understanding of the mechanisms underlying neuronal morphogenesis is essential for advancing our knowledge about neurodevelopmental disorders, such as autism spectrum disorder.
Neuronal morphogenesis occurs relatively in early-stage of cortical development. The defects in these early steps largely affect the later steps, such as neural connection and activity. Recent studies using ASD animal models indicate the defects in neuronal morphogenesis, not only spine/synapse formation but also neurite formation. Thus, a more comprehensive understanding of neuronal morphogenesis is essential to understand the etiology of neurodevelopmental disorders.
Neurite formation is an early cellular event during cortical developments. The defects in this step affect many later steps, such as neural connectivity and activity. Therefore, the full understanding of the mechanisms underlying neuronal morphogenesis is essential for advancing our knowledge about neurodevelopmental disorders, such as autism spectrum disorder.
14-3-3 Functions in the Brain
The aim of this project is to clarify the functions of 14-3-3 proteins, especially 14-3-3epsilon, 14-3-3eta and 14-3-3gamma, in the brain. We are interested in the 14-3-3's roles in neuromorphogenesis, neural connectivity, neural activity, and neurobehavior, such as learning and memory and sociability.
We are interested in the mechanisms of pathogenesis of neurological diseases resulting from mutations or overexpression of these 14-3-3 proteins, such as Miller-Dieker syndrome, autism, and epilepsy.
14-3-3 is a multifunctional protein in multiple cellular events, such as cell proliferation, cancer, and apoptosis. We have worked on the 14-3-3 functions in brain development. 14-3-3 regulates multiple cellular steps during cortical development from neurogenesis to neural activity.
We have worked on 14-3-3 functions in cortical development for a long time, but 14-3-3 is a mysterious protein, not only its name but also its functions. We still don't know a lot about 14-3-3.
We are interested in the mechanisms of pathogenesis of neurological diseases resulting from mutations or overexpression of these 14-3-3 proteins, such as Miller-Dieker syndrome, autism, and epilepsy.
14-3-3 is a multifunctional protein in multiple cellular events, such as cell proliferation, cancer, and apoptosis. We have worked on the 14-3-3 functions in brain development. 14-3-3 regulates multiple cellular steps during cortical development from neurogenesis to neural activity.
We have worked on 14-3-3 functions in cortical development for a long time, but 14-3-3 is a mysterious protein, not only its name but also its functions. We still don't know a lot about 14-3-3.
Gene Therapy using CRISPR/Cas9 technology
The field of gene therapy for neurological diseases is undergoing rapid development. In the early stages of the trial, it appears to be a promising option for treating certain neurological disorders. Several diseases can be treated with gene therapy, but research is ongoing to better understand how it works. In early results, gene therapy appears to be safe and well tolerated by most patients. Further research is needed to assess gene therapy's effectiveness in treating neurological disorders. Also, more research is required to understand gene therapy's long-term effects. In addition, further research is needed to develop a delivery system that can deliver gene therapy effectively. Lastly, more research is needed to identify potential risks associated with gene therapy. These efforts are crucial for progress.in treating neurological diseases.
In gene therapy, CRISPR technology offers precise and targeted modifications to the genetic code. It could enhance the safety and effectiveness of treatments for neurological diseases. In addition to enabling the correction of genetic mutations with high specificity, CRISPR may significantly advance the development of therapies for disorders. However, CRISPR is still being explored in clinical settings, and further research is required to fully understand its long-term effects and risks.
Our lab has been developing CRISPR-based gene therapy for psychiatric disorders, such as autism spectrum disorder (ASD). We are evaluating the efficacy of CRISPR in different models and studying its therapeutic potential. We hope that this study will lead to better and safer treatments for ASD and other psychiatric disorders.
