Back to the origins: Human brain organoids to investigate neurodegeneration

Neurodegenerative disorders represent a high burden in terms of individual, social and economical resources. No ultimate therapy has been established so far; human brain morphology and development can not be entirely reproduced by animal models, and genomic, metabolic and biochemical differences might contribute to a limited predictive power for human translation. Thus, the development of human brain organoid models holds a wide potential to investigate the range of physiological and pathological features that characterise the early onset of the degeneration. Moreover, central nervous system development has gained a crucial role in the study of the pathogenesis of neurodegenerative disorders. Premature alterations during brain maturation have been related to late disease manifestations; genetic mutations responsible for neurodegeneration have been found in genes highly expressed during neural development. Elucidating the mechanisms triggering neuronal susceptibility to degeneration is crucial for pathogenetic studies and therapeutic discoveries. In the present work, we provide an overview on the current applications of human brain organoids towards studies of neurodegenerative diseases, with a survey on the recent discoveries and a closing discussion on the present challenges and future perspectives.