Exploring the role of autophagy in shaping human brain development

Abstract

The human brain stands out for its advanced cognitive abilities, yet its overall structure remains surprisingly similar to that of other species, indicating a shared developmental blueprint. What distinguishes Homo sapiens are specific neuronal traits and subtle changes in brain organization that support complex behaviors and higher thinking. Comparative studies between modern humans and extinct human relatives, such as Neanderthals and Denisovans, show that although brain size was comparable, differences in structure and development led to distinct cognitive outcomes. These evolutionary changes helped shape the unique features of the modern human brain. At the same time, the human brain is marked by increased sensitivity to genetic disruptions. Many genes involved in brain development are conserved across species, and mutations in these genes often result in similar effects. However, human brain development shows a particular vulnerability to such defects, contributing to the risk of neurodevelopmental disorders (NDDs) like autism, epilepsy, and schizophrenia. Experimental tools such as induced pluripotent stem cell (iPSC) models are now essential for studying species-specific brain development. These models replicate early human brain formation and help uncover the mechanisms behind cognitive evolution. One key process under investigation is autophagy—a cellular recycling system—which may play a role in both the evolutionary refinement of the human brain and the origin of certain NDDs when disrupted.