Article
Biochemistry & Molecular Biology
Yuka Takahashi, Chikara Abe, Masaya Hane, Di Wu, Ken Kitajima, Chihiro Sato
Summary: Schizophrenia is a severe psychiatric disorder influenced by genetic and environmental factors. Changes in polysialylation of neural cell adhesion molecules have been found in the brains of patients with psychiatric disorders. This study investigates the effects of genetic (G) and environmental (E) factors on polysialylated NCAM expression using a schizophrenia mouse model and acute stress conditions. The study discovers differences in polysialylation and NCAM responses to stress in different brain regions, suggesting the vulnerability of the schizophrenia mouse model to stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Behavioral Sciences
Yu-Ming Chen, Chieh-Hsin Lin, Hsien-Yuan Lane
Summary: The study found that patients with schizophrenia had lower levels of DISC1 mRNA compared to healthy individuals, and that patients with lower DISC1 mRNA levels were more likely to exhibit more severe symptoms, including positive, negative, and depressive symptoms.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2022)
Article
Medicine, Research & Experimental
Ingrid Fricke-Galindo, Blanca E. Perez-Aldana, Luis R. Macias-Kauffer, Susana Gonzalez-Arredondo, David Davila-Ortiz De Montellano, Carlos L. Avina-Cervantes, Marisol Lopez-Lopez, Yaneth Rodriguez-Agudelo, Nancy Monroy-Jaramillo
Summary: This study evaluated the association of genetic variants in COMT, PRODH, and DISC1 with cognitive performance in Mexican-Mestizo adult patients with schizophrenia. The results showed that COMT rs4633 was related to overall cognitive assessment, while PRODH rs2870984 was associated with processing speed, working memory, verbal learning, and social cognition.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Saba Habibi, Mohammad Yaghoubzad-Maleki, Emran Heshmati, Khosrow Khalifeh
Summary: The development of schizophrenia and some other psychiatric disorders is related to defects in the normal functioning of DISC1. DISC1 is a large-sized protein that interacts with various proteins. Ndel1, on the other hand, interacts with DISC1 and plays a role in nervous system development. Mutations on DISC1 have clinical implications.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Chuan-Ching Lai, Rathinasamy Baskaran, Chih-Yu Tsao, Li-Heng Tuan, Pei-Fen Siow, Mahalakshmi Palani, Lukas Jyuhn-Hsiarn Lee, Chih-Min Liu, Hai-Gwo Hwu, Li-Jen Lee
Summary: Schizophrenia usually manifests during adolescence to young adulthood, providing an opportunity for early intervention. This study investigated the preventive effect of chronic N-acetylcysteine (NAC) treatment on the outbreak of psychosis in Disc1 Het mice and found that NAC can normalize biochemical and morphological features in the striatum. The findings not only support the use of NAC as a dietary supplement for schizophrenia prodromes, but also contribute to our understanding of potential therapeutic targets for treating mental disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cell Biology
Angelika B. Harbauer, Thomas L. Schwarz
Summary: In this study, the authors found that axonal mitophagy relies on local translation of Pink1 mRNA. The co-transport of Pink1 mRNA with mitochondria in neurons plays a crucial role in mitophagy in the distal parts of the cell. This finding contributes to our understanding of mitochondrial homeostasis in neurons.
Review
Biochemistry & Molecular Biology
Iveta Fizikova, Jozef Dragasek, Peter Racay
Summary: The complexity of the brain can lead to the development of serious neuropsychiatric disorders, such as schizophrenia. The etiopathogenesis of schizophrenia involves multiple mechanisms, highlighting its complexity and providing a new perspective for studying this disorder. This review focuses on the contribution of mitochondria, particularly oxidative damage, ROS, and energy metabolism. It also discusses the role of redox imbalance and lactate in oxidative stress, lipid peroxidation, and cognitive functions in schizophrenia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Komal Panchal, Anand Krishna Tiwari
Summary: Miro protein plays a crucial role in mitochondrial axonal transport, neuronal energy supply, and neuronal survival, and is closely associated with the pathogenesis of various neurodegenerative diseases. Therefore, Miro protein may serve as a potential target for the treatment of various neurodegenerative diseases.
Article
Multidisciplinary Sciences
Yinsuo Zhao, Eli Song, Wenjuan Wang, Chung-Han Hsieh, Xinnan Wang, Wei Feng, Xiangming Wang, Kang Shen
Summary: The trafficking of mitochondria into dendrites and axons is essential in the physiology and pathophysiology of neurons. Metaxin-1 and metaxin-2 play a crucial role in mitochondrial transport, forming complexes with Miro and motor proteins to facilitate movement along microtubules. These proteins have evolutionarily conserved functions and are required for proper mitochondrial trafficking in both C. elegans and human neurons.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Biomedical
Ivan A. Kuznetsov, Andrey V. Kuznetsov
Summary: Recent publications have shown that although mitochondria in axons can be rapidly replaced, the axons still contain older mitochondria. This study developed a model to simulate mitochondria distribution and age when a portion of returning mitochondria is redirected back into the axon. The findings suggest that reducing the percentage of stationary mitochondria can decrease their mean age, and the number of axon compartments can affect the age of stationary mitochondria.
INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Sumiko Kiryu-Seo, Reika Matsushita, Yoshitaka Tashiro, Takeshi Yoshimura, Yohei Iguchi, Masahisa Katsuno, Ryosuke Takahashi, Hiroshi Kiyama
Summary: The study reveals that proteasome-sensitive disassembly of the axon initial segment (AIS) may be a critical response for damaged motor neurons to temporarily transition to an immature state and meet energy demands.
Article
Microbiology
Simona Amodeo, Irina Bregy, Anneliese Hoffmann, Albert Fradera-Sola, Mara Kern, Helene Baudouin, Benoit Zuber, Falk Butter, Torsten Ochsenreiter
Summary: Trypanosoma brucei is a single-celled eukaryotic parasite with a unique mitochondrial genome called kinetoplast DNA (kDNA). The kDNA is physically linked to the basal body via the Tripartite Attachment Complex (TAC) to ensure its proper inheritance. In this study, we identified TbmtHMG44 and TbKAP68 as novel candidates that connect the TAC to the kDNA. Depletion of TbmtHMG44 or TbKAP68 leads to kDNA loss without missegregation, indicating their importance in maintaining the stability of the kDNA-TAC interface. These findings suggest that TbmtHMG44 and TbKAP68 form a distinct complex between the kDNA and TAC.
Article
Biology
Georgina Kontou, Pantelis Antonoudiou, Marina Podpolny, Blanka R. Szulc, I. Lorena Arancibia-Carcamo, Nathalie F. Higgs, Guillermo Lopez-Domenech, Patricia C. Salinas, Edward O. Mann, Josef T. Kittler
Summary: The study explores the role of Miro1 in PV+ interneurons and how changes in mitochondrial trafficking could alter network activity in the mouse brain. Impairments in Miro1-directed trafficking in PV+ interneurons altered their mitochondrial distribution and axonal arborization, while PV+ interneuron-mediated inhibition remained intact. These changes were accompanied by an increase in hippocampal gamma-oscillation frequency and promoted anxiolysis. Our findings show that precise regulation of mitochondrial dynamics in PV+ interneurons is crucial for proper neuronal signaling and network synchronization.
Article
Psychiatry
Agnes Espana, Henrik Seth, Julie Jezequel, Tingting Huang, Delphine Bouchet, Marylin Lepleux, Helene Grea, Karl Bechter, Marion Schneider, Eric Hanse, Laurent Groc
Summary: The dysfunction of NMDAR trafficking is consistently found in clinically relevant models of psychosis, offering new therapeutic strategies. Artificial manipulations of NMDAR surface dynamics can regulate the adult acoustic startle reflex in rats exposed to early pathological challenges.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Maria Guardiola-Ripoll, Alejandro Sotero-Moreno, Carmen Almodovar-Paya, Noemi Hostalet, Amalia Guerrero-Pedraza, Nuria Ramiro, Jordi Ortiz-Gil, Barbara Arias, Merce Madre, Joan Soler-Vidal, Raymond Salvador, Peter J. McKenna, Edith Pomarol-Clotet, Mar Fatjo-Vilas
Summary: This study investigated the brain correlates of DISC1 haplotypes associated with schizophrenia (SZ) through a functional neuroimaging genetics approach. The results showed that DISC1 haplotypes modulated working memory-related brain activity in regions such as the ventrolateral and dorsolateral prefrontal cortices.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Bo Kyoung Suh, Seol-Ae Lee, Cana Park, Yeongjun Suh, Soo Jeong Kim, Youngsik Woo, Truong Thi My Nhung, Su Been Lee, Dong Jin Mun, Bon Seong Goo, Hyun Sun Choi, So Jung Kim, Sang Ki Park
Summary: Mitochondrial movement in neurons is tightly regulated by dysbindin, a factor associated with schizophrenia, which influences the distribution and transport of mitochondria along axons and affects calcium dynamics in presynaptic terminals.
Article
Psychiatry
Su Been Lee, Jihyun Park, Yongdo Kwak, Young-Un Park, Truong Thi My Nhung, Bo Kyoung Suh, Youngsik Woo, Yeongjun Suh, Eunbyul Cho, Sehyung Cho, Sang Ki Park
Summary: DISC1 plays a crucial role in regulating neuronal activity and circadian rhythm by inhibiting GSK3 beta activity and affecting BMAL1 stability. Deficiency of Disc1 results in decreased expression of circadian genes and disrupted circadian physiology and behaviors in mice.
TRANSLATIONAL PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
You-Me Kim, Eui-Cheol Shin
Summary: Researchers have reviewed how SARS-CoV-2 manipulates the immune system by inhibiting host IFN responses, leading to delayed and exaggerated inflammation, which contributes to the severity of COVID-19. Further investigations are needed to better understand the mechanisms behind these immune system dysfunctions caused by the virus.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Biology
Soo Jeong Kim, Youngsik Woo, Hyun Jin Kim, Bon Seong Goo, Truong Thi My Nhung, Seol-Ae Lee, Bo Kyoung Suh, Dong Jin Mun, Joung-Hun Kim, Sang Ki Park
Summary: This study identifies the role of the protein Rai14 in the regulation of dendritic spine dynamics and its association with stress-induced depressive-like behaviors. Rai14-deficient neurons exhibit reduced dendritic spine density and impaired synaptic activity. Rai14 forms a complex with Tara, preventing its degradation and accumulating in the dendritic spine neck, enhancing spine maintenance. Rai14 deficiency also alters gene expression relevant to depression and increases depressive-like behaviors.
Article
Chemistry, Multidisciplinary
Donggyu Lee, Youngsik Woo, Ji-seon Lim, Ikbum Park, Sang Ki Park, Joon Won Park
Summary: In this study, a neurological protein was quantified in a single cell using atomic force microscopy (AFM). The captured DISC1 protein was visualized through force mapping with AFM. The average number of DISC1 in a cell was found to be 4.38 x 10(3), consistent with the ensemble-averaged value. This AFM approach can be useful for studying protein behavior and tracking physiological changes in individual cells.
Article
Biochemistry & Molecular Biology
Indira Singaram, Ashutosh Sharma, Shashank Pant, Muyun Lihan, Mi-Jeong Park, Melissa Pergande, Pawanthi Buwaneka, Yusi Hu, Nadim Mahmud, You-Me Kim, Stephanie Cologna, Vladimir Gevorgyan, Irum Khan, Emad Tajkhorshid, Wonhwa Cho
Summary: Membrane lipids control the cellular activity of kinases containing the SH2 domain. In this study, new nonlipidic small molecule inhibitors of the lipid-SH2 domain interaction were developed to block the cellular activity of their host proteins. The research shows that targeting lipid-protein interaction is a powerful approach to developing new small molecule drugs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bon Seong Goo, Dong Jin Mun, Seunghyun Kim, Truong Thi My Nhung, Su Been Lee, Youngsik Woo, Soo Jeong Kim, Bo Kyoung Suh, Sung Jin Park, Hee-Eun Lee, Kunyou Park, Hyunsoo Jang, Jong-Cheol Rah, Ki-Jun Yoon, Seung Tae Baek, Seung-Yeol Park, Sang Ki Park
Summary: This study investigates the association between MAD1L1 and schizophrenia and identifies the molecular mechanisms underlying this association. The researchers found that MAD1 plays a crucial role in neuronal development and is involved in neuronal migration and neurite outgrowth. MAD1 also regulates vesicular trafficking from the Golgi apparatus to the plasma membrane, which is essential for neuronal polarity. The findings suggest that alterations in MAD1 may contribute to the pathobiology of schizophrenia.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Eunbyul Cho, Youngsik Woo, Yeongjun Suh, Bo Kyoung Suh, Soo Jeong Kim, Truong Thi My Nhung, Jin Yeong Yoo, Tran Diem Nghi, Su Been Lee, Dong Jin Mun, Sang Ki Park
Summary: The authors developed a MAM-specific BRET-based Ca2+ indicator called MAM-Calflux, which serves as both a Ca2+ indicator and a structural marker. It can estimate steady-state MAM Ca2+ levels and visualize abnormally accumulated MAM Ca2+ in Parkinson's disease mouse model. MAM-Calflux can be a versatile tool for ratiometric measurement of dynamic inter-organellar Ca2+ communication.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Truong Thi My Nhung, Nguyen Phuoc Long, Tran Diem Nghi, Yeongjun Suh, Nguyen Hoang Anh, Cheol Woon Jung, Hong Minh Triet, Minkyo Jung, Youngsik Woo, Jinyeong Yoo, Sujin Noh, Soo Jeong Kim, Su Been Lee, Seongoh Park, Gary Thomas, Thomas Simmen, Jiyoung Mun, Hyun-Woo Rhee, Sung Won Kwon, Sang Ki Park
Summary: Mitochondria-associated ER membranes (MAMs), formed by the endoplasmic reticulum (ER) and mitochondria, play an important role in maintaining calcium homeostasis and neurotransmitter release in the neuronal system. The kinase CK2A1 and its interaction with PACS2 regulate the composition and calcium transport of MAMs. Mutations in PACS2 associated with developmental and epileptic encephalopathy disrupt MAM integrity, leading to impaired mitochondrial calcium uptake and increased cytosolic calcium levels, ultimately causing abnormal neurotransmitter release.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Young-Chan Kim, Ji Hoon Ahn, Hokyung Jin, Myung Jin Yang, Seon Pyo Hong, Jin-Hui Yoon, Sang-Hoon Kim, Tirhas Niguse Gebre, Hyuek Jong Lee, You-Me Kim, Gou Young Koh
Summary: Neonatal susceptibility to meningitis may be due to the immature central nervous system (CNS) barrier. By studying the propagation of lymphocytic choriomeningitis virus (LCMV) in the CNS, it was found that neonatal mice have a higher mortality rate after infection, and the virus can breach the dura mater and reach the leptomeninges, choroid plexus, and cerebral cortex. Neonatal dural immune cells were found to be immature and mainly composed of CD206(hi) macrophages, while adult perivenous sinus immune cells were enriched in MHCII(hi) macrophages that produce antiviral molecules and protect the CNS from systemic virus invasion.
SCIENCE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Dong Jin Mun, Bon Seong Goo, Bo Kyoung Suh, Ji-Ho Hong, Youngsik Woo, Soo Jeong Kim, Seunghyun Kim, Su Been Lee, Yubin Won, Jin Yeong Yoo, Eunbyul Cho, Eun Jin Jang, Truong Thi My Nhung, Hong Minh Triet, Hongyul An, Haeryun Lee, Minh Dang Nguyen, Seung-Yeol Park, Seung Tae Baek, Sang Ki Park
Summary: In this study, the Gcap14-Ndel1 complex is identified as a fundamental regulator of cytoskeletal remodeling during neurodevelopment, including neuronal process elongation and migration. Deficiency of Gcap14 leads to impaired cortical lamination and defective neuronal migration. The interaction between Gcap14 and Ndel1 effectively corrects the downregulation of microtubule dynamics and the defects in neuronal migration caused by Gcap14 deficiency.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Jihong Bae, Kwangcheon Park, You-Me Kim
Summary: Cancer is a leading cause of death globally, and the number of cancer patients is expected to continue increasing. Traditional cancer therapies have largely ignored the role of the immune system in eliminating cancer cells, but recent understanding of immunological mechanisms has led to the development of immunotherapies that have revolutionized cancer treatment. However, only a small proportion of patients respond to immunotherapy, and one critical factor in determining the success of immunotherapy is the commensal microbiota inhabiting patients. The functional diversity of the microbiota can differentially affect the host immune system and control the efficacy of immunotherapy in individual cancer patients. Clinical studies have shown that changing the gut microbiota composition through fecal microbiota transplantation can convert non-responders to responders of the same therapy. Therefore, extensive efforts are being made to identify and develop specific bacteria or bacteria mixtures for cancer immunotherapy.
Review
Biochemistry & Molecular Biology
Seongryong Kim, Hyun-Sup Song, Jihyun Yu, You-Me Kim
Summary: The MiT family proteins are evolutionarily conserved transcription factors that play essential roles in regulating cellular functions. They are best known for their involvement in lysosome biogenesis and autophagy induction, while also having effects on cellular metabolism, mitochondrial dynamics, and stress responses. Each MiT family member plays distinct or redundant roles in different immune cell types, and there is still much to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.
MOLECULES AND CELLS
(2021)