Cancers doi: 10.20517/and.2025.11

Authors: Yiming Jiang,Junwei Lu,Jieli Li

Against the backdrop of global population aging, prostate cancer (PCa), as one of the most common malignant tumors in elderly men, has an association with cognitive frailty (CF) that has garnered increasing attention. CF significantly elevates the risk of adverse health outcomes such as dementia, falls, disability, and mortality in elderly PCa patients. This review systematically summarizes the existing evidence regarding assessment tools, underlying mechanisms, and intervention strategies for CF in elderly PCa patients. Currently, there is no gold standard for PCa-specific CF assessment. The pathogenesis of CF involves complex interactions among multiple pathways: age-related physiological decline, chronic systemic inflammation induced by PCa and its treatments, neuroendocrine dysregulation, oxidative stress, blood-brain barrier impairment, and psychosocial factors. Interventions for CF encompass non-pharmacological strategies and emerging pharmacological treatments. However, these approaches face challenges, including undefined optimal protocols, poor long-term adherence, and insufficient clinical validation. Future research should focus on: developing and validating integrated CF assessment tools tailored for PCa patients; elucidating the molecular mechanisms of CF in the context of PCa; designing and validating personalized, multimodal intervention regimens; bridging the digital divide to advance clinical translation of digital health technologies; rigorously evaluating the benefit-risk profiles of pharmacological interventions through large-scale, long-term clinical trials. Addressing CF in elderly PCa patients is crucial for optimizing disease management, improving quality of life, and guiding targeted clinical interventions.

Cancers doi: 10.20517/and.2025.29

Authors: Wenhao Yang,Zhu Yu,Wei Wang,Sen Yan

Since the first report of Alzheimer’s disease (AD) in 1906, scientists have made remarkable progress in elucidating its molecular mechanisms, pathogenic processes, and core neuropathological features. However, effective therapeutic strategies for AD remain elusive, and the disease is still fundamentally incurable. The use of animal models constitutes a critical step in investigating pathological mechanisms and conducting preclinical experiments. With advances in transgenic technology, a variety of mouse models have been developed to replicate the pathological changes, as well as cognitive and motor impairments, observed in AD patients. These models have played a pivotal role in studying the pathogenesis of AD and screening potential therapeutic approaches. For example, the Tg2576 mouse model can simulate AD-related pathological alterations, including β-amyloid (Aβ) plaque deposition, neuroinflammation, and cognitive impairment. Nevertheless, mouse models have limitations in mimicking the complex pathology and clinical manifestations of human AD. In contrast, some medium- to large-sized animals in nature, such as canines and non-human primates (NHPs), can spontaneously develop AD-like pathological changes. For instance, NHPs exhibit high similarity to humans in terms of brain structure and function, and their spontaneous AD-like pathological changes provide a more human-relevant model for investigating AD pathogenesis and drug screening. This article elaborates on the pathological characteristics, clinical manifestations, advantages, and disadvantages of five distinct animal models (mouse, cat, dog, sheep and NHPs) in experimental research, thereby providing a reference for model selection in AD studies.

Cancers doi: 10.20517/and.2025.16

Authors: Huiyue Chen,Lu Cao,Siyu Liu,Kai Yuan

The dynamic relationship between neuronal activity and mitochondrial function plays a crucial role in cognitive health, with disruptions linked to age-related cognitive decline. In this mini review, we highlight the significant findings of Li et al., who discovered an age-dependent coupling mechanism between neuronal/synaptic excitation and excitation-dependent mitochondrial gene transcription coupling (E-TC_mito). Their research revealed that enhancing brain E-TC_mito in aged animals effectively mitigated age-related cognitive decline.

Cancers doi: 10.20517/and.2025.22

Authors: Irving Christian Rodríguez-González,Fernando Botello-Villagrana,Sergio Ruben Gomez-Villalobos,Arnulfo González-Cantú,Ximena Monserrat Torres-Mancilla,Francisco Alejandro Luna-Rangel,Brenda Gonzalez-Bedolla,Elly Robles,Mirna González-González,Daniel Martinez-Ramirez

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide and is characterized by progressive motor and non-motor manifestations. Its rising prevalence poses significant challenges for clinical management and public health. Type 2 diabetes mellitus (T2DM), the most frequent metabolic disorder, shares several pathogenic mechanisms with PD, including mitochondrial dysfunction, insulin resistance, and oxidative stress. Epidemiological studies suggest a higher incidence of PD among individuals with T2DM, with growing evidence that diabetes may accelerate the onset and progression of motor and cognitive symptoms. This narrative review summarizes current knowledge on the relationship between T2DM and PD, with emphasis on epidemiological associations, shared biological pathways, and the therapeutic implications of antidiabetic agents. Available data indicate that patients with both PD and T2DM tend to experience a faster progression of motor and cognitive decline. Clinical trials assessing hypoglycemic agents have reported heterogeneous findings: pioglitazone failed to demonstrate neuroprotective effects, while exenatide showed temporary improvements in motor function that were not sustained after treatment discontinuation. Experimental studies also suggest possible neuroprotective actions of metformin and dipeptidyl peptidase 4 inhibitors, although well-designed clinical trials are still lacking. The interaction between T2DM and PD highlights the importance of metabolic factors in neurodegeneration. Further studies are required to determine the impact of diabetes and its treatments on the PD course and to explore antidiabetic drugs as potential disease-modifying therapies.

Cancers doi: 10.20517/and.2025.26

Authors: Ahsan Habib,Gavin Riccobono,Lulu Tian,Disa Basu,Lixin Sun,Lisa Chang,Victor M. Martinez Smith,Lupeng Wang,Weidong Le,Huaibin Cai

Aim: Define the subtype-specific contributions of nigrostriatal dopaminergic neurons (DANs) to motor and non-motor behaviors by comparing Calbindin 1-positive (Calb1⁺) and Aldehyde dehydrogenase 1a1-positive (Aldh1a1⁺) DANs.

Methods: Intersectional genetic strategy and chemogenetic inhibition were applied to selectively silence Calb1⁺ or Aldh1a1⁺ DANs in mice. An adeno-associated viral vector (AAV-CreOn-FlpOn-hM4Di-P2A-mCherry) was stereotactically delivered into the substantia nigra pars compacta of double knock-in lines Th^Flp; Calb1^IRESCre or Th^Flp; Aldh1a1^CreERT2. Following expression, subtype-specific neuronal inhibition was induced with a designer receptor exclusively activated by designer drugs (DREADD) ligand, and the mice were assessed in assays of voluntary movement, motor skill learning, and early associative learning behavior.

Results: Chemogenetic inhibition of either Calb1⁺ or Aldh1a1⁺ DANs produced a marked reduction in voluntary movement and impaired acquisition of motor skills, indicating that both subtypes are necessary for normal motor function and learning. In contrast, only inhibition of Calb1⁺ DANs altered early associative-learning performance, revealing a dissociable, subtype-specific role for Calb1⁺ neurons in reinforcement-related behavior that was not observed with Aldh1a1⁺ neuron inhibition.

Conclusion: Both Calb1⁺ and Aldh1a1⁺ nigrostriatal DANs are key regulators of movement and motor learning, with Calb1⁺ neurons additionally modulating reward-based associative learning. These findings highlight the functional heterogeneity of nigrostriatal DAN subtypes and identify potential therapeutic targets for addressing motor and non-motor deficits in Parkinson’s disease.