Centrosomes and cilia in neurodegeneration: main actors or mere spectators? DOI Creative Commons
Ramona Lattao

Open Biology, Journal Year: 2025, Volume and Issue: 15(5)

Published: May 1, 2025

Centrosomes are intracellular organelles traditionally recognized as the primary microtubule (MT) organizing centres (MTOCs) in cell, playing a crucial role cytoskeleton and forming MT-based spindle during cell division. However, it is now well established that centrosomes also function central hubs for wide range of signalling pathways. In non-dividing cells, they give rise to cilium, surface antenna serves key structure signalling. Neurons highly specialized cells with distinctive morphology, most neurons have cilia. During brain development, cilia regulate self-renewal neural progenitors, differentiation, migration synapse formation newly generated neurons. As consequence, defects result various neurodevelopmental disorders. The neurodegeneration, or progressive loss neurons, less understood. take part several cellular processes often disrupted neurodegenerative diseases (NDDs), many proteins associated these conditions been found at suggesting link between underlying mechanisms contribute neuronal decline. Unravelling if how centrosome dysfunction contributes neurodegeneration could significantly deepen our understanding biology Such insights may pave way new therapeutic approaches address debilitating conditions.

Language: Английский

Age-related ciliopathy: Obesogenic shortening of melanocortin-4 receptor-bearing neuronal primary cilia DOI Creative Commons
Manami Oya, Yoshiki Miyasaka, Yoshiko Nakamura

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(5), P. 1044 - 1058.e10

Published: March 6, 2024

Obesity is often associated with aging. However, the mechanism of age-related obesity unknown. The melanocortin-4 receptor (MC4R) mediates leptin-melanocortin anti-obesity signaling in hypothalamus. Here, we discovered that MC4R-bearing primary cilia hypothalamic neurons progressively shorten age rats, correlating age-dependent metabolic decline and increased adiposity. This "age-related ciliopathy" promoted by overnutrition-induced upregulation inhibited or reversed dietary restriction knockdown ciliogenesis-associated kinase 1 (CILK1). Forced shortening genetic approaches impaired neuronal sensitivity to melanocortin resulted decreased brown fat thermogenesis energy expenditure appetite, finally developing leptin resistance. Therefore, despite its acute effect, chronic increases susceptibility promoting cilia. study provides a crucial for obesity, which risk syndrome.

Language: Английский

Citations

16
Ultrastructural differences impact cilia shape and external exposure across cell classes in the visual cortex DOI Creative Commons
Carolyn Ott, Russel Torres, T. S. Kuan

et al.

Current Biology, Journal Year: 2024, Volume and Issue: 34(11), P. 2418 - 2433.e4

Published: May 14, 2024

A primary cilium is a membrane-bound extension from the cell surface that contains receptors for perceiving and transmitting signals modulate state activity. Primary cilia in brain are less accessible than on cultured cells or epithelial tissues because they protrude into deep, dense network of glial neuronal processes. Here, we investigated frequency, internal structure, shape, position large, high-resolution transmission electron microscopy volumes mouse visual cortex. Cilia extended bodies nearly all excitatory inhibitory neurons, astrocytes, oligodendrocyte precursor (OPCs) but were absent oligodendrocytes microglia. Ultrastructural comparisons revealed base microtubule organization differed between neurons glia. Investigating cilia-proximal features many directly adjacent to synapses, suggesting poised encounter locally released signaling molecules. Our analysis indicated synapse proximity likely due random encounters neuropil, with no evidence activity as would be expected tetrapartite synapses. The observed class differences synapses largely external length. Many key structural influenced both placement shape and, thus, exposure processes outside cilium. Together, ultrastructure within around suggest formation function across types brain.

Language: Английский

Citations

10
Primary cilia promote the differentiation of human neurons through the WNT signaling pathway DOI Creative Commons
Andrea Coschiera, Masahito Yoshihara, Gilbert Lauter

et al.

BMC Biology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 27, 2024

Primary cilia emanate from most human cell types, including neurons. Cilia are important for communicating with the cell's immediate environment: signal reception and transduction to/from ciliated cell. Deregulation of ciliary signaling can lead to ciliopathies certain neurodevelopmental disorders. In developing brain play well-documented roles expansion neural progenitor pool, while information about during post-mitotic neuron differentiation maturation is scarce.

Language: Английский

Citations

9
The Primary Cilia are Associated with the Axon Initial Segment in Neurons DOI Creative Commons
Han Wang, Yu Li, Xin Li

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract The primary cilia serve as pivotal mediators of environmental signals and play crucial roles in neuronal responses. Disruption ciliary function has been implicated circuit disorders aberrant excitability. However, the precise mechanisms remain elusive. To study link between excitability, manipulation somatostatin receptor 3 (SSTR3) is investigated, an example how alterations signaling may affect activity. It found that SSTR3 expression perturbed not only morphology but also disrupted cascades. Genetic deletion resulted spatial memory synaptic plasticity. axon initial segment (AIS) a specialized region where action potentials are initiated. Interestingly, loss led to decrease Akt‐dependent cyclic AMP‐response element binding protein (CREB)‐mediated transcription at AIS, specifically downregulating AIS master organizer adaptor ankyrin G (AnkG) expression. In addition, other proteins serotonin 6 (5‐HT6R)and intraflagellar transport 88 (IFT88) induced length changes AIS. findings elucidate specific interaction providing insight into impact on excitability integrity.

Language: Английский

Citations

1
Nanometer-scale views of visual cortex reveal anatomical features of primary cilia poised to detect synaptic spillover DOI Creative Commons
Carolyn Ott, Russel Torres, T. S. Kuan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 1, 2023

A primary cilium is a thin membrane-bound extension off cell surface that contains receptors for perceiving and transmitting signals modulate state activity. While many types have cilium, little known about cilia in the brain, where they are less accessible than on cultured cells or epithelial tissues protrude from bodies into deep, dense network of glial neuronal processes. Here, we investigated frequency, internal structure, shape, position large, high-resolution transmission electron microscopy volumes mouse visual cortex. Cilia extended nearly all excitatory inhibitory neurons, astrocytes, oligodendrocyte precursor (OPCs), but were absent oligodendrocytes microglia. Structural comparisons revealed membrane structure at base microtubule organization differed between neurons glia. OPC distinct shortest contained pervasive vesicles only occasionally observed neuron astrocyte cilia. Investigating cilia-proximal features directly adjacent to synapses, suggesting well poised encounter locally released signaling molecules. proximity synapses was random, not enriched, synapse-rich neuropil. The anatomy, including changes centriole location, defined key structural placement shape. Together, anatomical insights both within around glia provide new formation function across brain.

Language: Английский

Citations

21
The extracellular matrix as modifier of neuroinflammation and recovery in ischemic stroke and intracerebral hemorrhage DOI Creative Commons
Hongmin Li, Samira Ghorbani, Chang‐Chun Ling

et al.

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 186, P. 106282 - 106282

Published: Sept. 6, 2023

Stroke is the second leading cause of death worldwide and has two major subtypes: ischemic stroke hemorrhagic stroke. Neuroinflammation a pathological hallmark intracerebral hemorrhage (ICH), contributing to extent brain injury but also in its repair. intricately linked extracellular matrix (ECM), which profoundly altered after aging. In early stages ICH, immune cells are involved deposition remodeling ECM thereby affecting processes such as blood-brain barrier cellular integrity. components regulate leukocyte infiltration into central nervous system, activate variety cells, induce elevation metalloproteinases (MMPs) turn, excessive MMPs may degrade that pro-inflammatory injurious. Conversely, later stroke, several molecules contribute tissue recovery. For example, thrombospondin-1 biglycan promote activity regulatory T inhibit synthesis proinflammatory cytokines, aid regenerative processes. We highlight these roles ICH discuss their potential molecular mechanisms. Finally, we therapeutics could be considered normalize Our goal spur research on order improve prognosis ICH.

Language: Английский

Citations

17
Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases DOI Creative Commons
Siwei Chu,

Xinyi Xie,

Carla Payan

et al.

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Aug. 7, 2023

Abstract The AAA + ATPase valosin containing protein (VCP) is essential for cell and organ homeostasis, especially in cells of the nervous system. As part a large network, VCP collaborates with many cofactors to ensure proteostasis under normal, stress, disease conditions. A number mutations have revealed importance human health. In particular, facilitates dismantling aggregates removal dysfunctional organelles. These are critical events prevent malfunction brain other parts line this idea, mutants linked onset progression neurodegeneration diseases. intricate molecular mechanisms that connect distinct pathologies continue be uncovered. Emerging evidence supports model controls cellular functions on multiple levels type specific fashion. Accordingly, derail homeostasis through several can instigate disease. Our review focuses association between neurodegeneration. We discuss latest insights field, emphasize open questions, speculate potential as drug target some most devastating forms

Language: Английский

Citations

16
Lipid and glucose metabolism in senescence DOI Creative Commons
Bin Liu,

Qingfei Meng,

Xin Gao

et al.

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: Aug. 23, 2023

Senescence is an inevitable biological process. Disturbances in glucose and lipid metabolism are essential features of cellular senescence. Given the important roles these types metabolism, we review evidence for how key metabolic enzymes influence senescence senescence-related secretory phenotypes, autophagy, apoptosis, insulin signaling pathways, environmental factors modulate homeostasis. We also discuss alterations abnormal diseases anti-cancer therapies that target through interventions. Our work offers insights developing pharmacological strategies to combat cancer.

Language: Английский

Citations

16
Dystrophin 71 deficiency causes impaired aquaporin-4 polarization contributing to glymphatic dysfunction and brain edema in cerebral ischemia DOI Creative Commons
Jian Yang, Chang Cao, Jiale Liu

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 199, P. 106586 - 106586

Published: June 29, 2024

Language: Английский

Citations

6
Primary cilia signaling in astrocytes mediates development and regional-specific functional specification DOI
Lizheng Wang, Qianqian Guo,

Sandesh Acharya

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(9), P. 1708 - 1720

Published: Aug. 5, 2024

Language: Английский

Citations

5