Mapping Neurodegeneration and Brain Aging: Tools for a Mechanistic Understanding

TOPICAL COLLECTIONS

Guest Editors

Luis Oskar Soto Rojas

Universidad Nacional Autónoma de México (National Autonomous University of Mexico)

Dr. Oskar Soto is a medical doctor and early-career neuroscientist at UNAM’s Faculty of Higher Studies Iztacala, where he leads the Laboratory for Research in Neurosciences and Neurodegenerative Diseases (LINEN). His research focuses on Alzheimer’s and Parkinson’s disease, with emphasis on blood–brain barrier dysfunction, protein misfolding, neuroinflammation, oxidative stress, and mitochondrial impairment. He investigates how metabolic modulators and structured exercise influence key pathological processes, including blood–brain barrier integrity, tau and β-amyloid accumulation, cognition, and motor performance.He has authored more than 35 scientific publications (h-index 18; >1,300 citations), is the youngest medical doctor elected to the Mexican National Academy of Medicine, and has served as a reviewer for more than 15 international journals. He leads national and international collaborations funded by organizations such as IBRO and serves as the scientific coordinator of the MEDICI program, a clinical research initiative that has trained more than 600 medical students and health professionals.

Sandra Aurora Esquivel Niño

Department of Genetics and Molecular Biology, CINVESTAV-Zacatenco

Sandra A. Esquivel Niño is a principal investigator in the Laboratory of Synergistic Approaches for Neurodegeneration in the Department of Genetics and Molecular Biology at CINVESTAV–Zacatenco in Mexico City. Her research focuses on mitochondrial biology, aging, APOE-associated risk, and the cellular mechanisms underlying neurodegeneration. She integrates primary human cell models, fibroblasts, neuronal cultures, and multi-omics approaches to investigate mitochondrial dysfunction, lysosomal impairment, and intercellular mitochondrial transfer in Alzheimer’s disease and related disorders.Dr. Esquivel has experience in translational geroscience and population genetics and has contributed to international collaborations involving CINVESTAV, UCLA, IPICYT, and GERO–Chile. She also serves as a reviewer for Neurochemical Research and other journals. Her work emphasizes mechanistic discovery and innovative methodological approaches to understand vulnerability and resilience in brain aging.

Collection Overview

Neurodegenerative diseases and age-related cognitive decline remain among the most urgent scientific and clinical challenges of our time. Despite major advances, the mechanistic links between aging, cellular stress responses, metabolic dysfunction, and the progressive failure of neural circuits remain poorly understood. This topical collection aims to bring together cutting-edge methodologies that illuminate how molecular, cellular, and systems-level processes interact to drive neurodegeneration across the lifespan, with particular emphasis on neurovascular integrity, mitochondrial function, and metabolic resilience.

We invite contributions that showcase experimental workflows capable of dissecting mitochondrial dysfunction, proteostasis collapse, neuroinflammation, impaired autophagy-lysosomal pathways, blood-brain barrier breakdown, and senescence-related phenotypes in diverse models, including primary human cells, iPSC-derived lineages, organoids, animal models, clinical cohorts, and computational approaches. Methods that enable visualization, quantification, or manipulation of these pathways are particularly welcome, such as advanced imaging modalities (including confocal and super-resolution microscopy, MRI, PET, DCE-MRI, and other neuroimaging techniques), metabolic profiling, live-cell reporters, transcriptomic and proteomic pipelines. Given the growing interest in cell-cell communication and multicellular interactions in brain aging, protocols involving microglia, astrocytes, neurons, endothelial and pericyte populations, and cross-tissue metabolic signaling are strongly encouraged.

Submissions focusing on emerging technologies, such as organoid-based models, 3D culture systems, neuroimmune assays, in vivo imaging platforms, and tools to evaluate resilience or vulnerability to aging, including assays for neurovascular coupling, mitochondrial transfer, and metabolic modulation, are also invited. By assembling methodological contributions across these domains, this collection aims to provide an integrated experimental toolkit for researchers working to unravel the complexity of neurodegenerative processes. Ultimately, the issue seeks to highlight approaches that will accelerate mechanistic discovery and support the development of preventive and therapeutic strategies for age-associated neurological disorders, especially those rooted in mitochondrial and neurovascular dysfunction.