Overexpression of DYRK1A in down syndrome: Analysis of kinase activity

Targeting kinases in neurodegenerative diseases and cancer: Structural insights and therapeutic strategies.

SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives

Emerging evidence has expanded the functional repertoire of SKP2 beyond cell cycle control to encompass metabolism, DNA repair, stemness, tumor microenvironment and immunotherapy response, positioning it as an increasingly attractive target for intervention.

Targeting YWHAG protein: A unified therapeutic strategy against tumors or neurodegenerative diseases

YWHAG is a subtype of the 14-3-3 protein family that regulates the transduction of multiple signaling pathways in cells, such as the phosphoinositide 3-kinase–protein kinase B (PI3K-AKT) and mitogen-activated protein kinase (MAPK) pathways, by recognizing and binding to specific phosphorylated target protein motifs. These signaling pathways are widely found to be abnormally activated or shut down in human diseases, such as cancer and neurodegenerative diseases. Different evidence has shown that the expression levels and functions of YWHAG in different tumors are not the same. Meanwhile, the potential functions of YWHAG in these diseases and its role in regulating abnormal signaling pathways are still unknown. Therefore, further exploration and research are needed to determine YWHAG’s core role in regulating signaling pathways and whether YWHAG can be a therapeutic target for diseases to develop corresponding drugs. This review will revisit the structure and function of YWHAG, elaborate on the newly identified YWHAG-interacting proteins in recent years, summarize the functions of YWHAG in cancer while comparing it with the homologous family member YWHAZ, explore the functions of YWHAG in neurodegenerative diseases, and present our perspectives on drug-screening strategies targeting YWHAG.

PP2A: Decoding Its Structure, Regulation and Therapeutic Applications in Neurological Disorders.

Protein phosphatase 2A (PP2A) is a highly conserved serine/threonine phosphatase that plays a pivotal role in maintaining cellular homeostasis by counterbalancing kinase activity. As a heterotrimeric enzyme composed of scaffolding, regulatory, and catalytic subunits, PP2A achieves extraordinary functional diversity through the dynamic assembly of more than 80 holoenzyme variants. This structural versatility allows PP2A to regulate a wide range of biological processes, including cell cycle progression, apoptosis, DNA damage response, and major signaling pathways such as MAPK and Wnt. Dysregulation of PP2A, through altered subunit expression, post-translational modification, or inhibition by endogenous suppressors like CIP2A and SET, has been implicated in diverse diseases, notably neurodegenerative disorders, cancers, and metabolic syndromes. In neurological disorders such as Alzheimer's and Parkinson's diseases, impaired PP2A activity contributes to pathogenic protein hyperphosphorylation, neurofibrillary tangle formation, and neuroinflammation. Recent advances have fundamentally reshaped our understanding of PP2A biology. High-resolution structural studies have revealed the molecular basis of holoenzyme assembly and substrate recruitment, while accumulating evidence suggests that PP2A activity is dynamically regulated across tissues and cell types, largely driven by differential expression of regulatory subunits and post-translational modifications. Despite these advances, current knowledge remains fragmented, and a comprehensive synthesis linking PP2A structural dynamics, regulatory mechanisms, and its roles in pathophysiology, particularly in the context of neurological disorders, is still lacking. This review deciphers the structural complexity and regulatory mechanisms of PP2A, elucidates its multifaceted roles in neural physiology and pathology, and examines current and emerging therapeutic strategies targeting PP2A modulation to intervene in neurological disease.

Tumor suppressor BAP1 emerges as a key regulator of metabolism and cell death in tumors

An integrated overview of the molecular features and functional roles of BAP1 is provided, with particular emphasis on its impacts on the regulation of cell death including apoptosis, ferroptosis and disulfidptosis.

The Emerging Role of UCHL1 in Neurological and Musculoskeletal Diseases

Ubiquitin C‐terminal hydrolase L1 (UCHL1) is a highly conserved deubiquitinating enzyme that has transitioned from being viewed as a “brain‐specific” protein to a global regulator of cellular proteostasis and signal transduction. As a key component of the ubiquitin‐proteasome system (UPS), UCHL1 maintains the intracellular free ubiquitin pool through its C‐terminal hydrolase activity, while also exhibiting atypical ligase‐like functions and acting as a molecular scaffold for signaling complexes. Beyond its classical role in neurons, increasing evidence suggests that UCHL1 participates in diverse pathological conditions including neurodegeneration, cancer, cardiovascular and metabolic diseases, as well as musculoskeletal disorders. Through regulation of protein turnover, oxidative stress, inflammatory signaling, and cell survival, UCHL1 emerges as a context‐dependent regulator with dual protective and pathogenic roles. This review explores the sophisticated multi‐level regulation of UCHL1, ranging from transcriptional control to epigenetic silencing and posttranslational modifications, summarizes the recent research progress of UCHL1 in various systems, and elaborates on its mechanism of action in various conditions, including neurological and musculoskeletal disorders.