01Abnormal protein accumulation and aggregate formation are involved in the pathogenesis of various neurodegenerative diseases
Pathological analyses have shown abnormal protein accumulation in neural tissues of patients with various neurodegenerative diseases. These abnormal proteins are thought to form aggregates upon aging and various stresses, resulting in neurodegeneration. Therefore, many attempts have been made to develop therapeutics targeting the accumulation of these abnormal proteins. However, various findings have suggested that the accumulation of abnormal proteins alone is insufficient to explain the pathogenesis of neurodegeneration. To overcome neurodegenerative diseases, we believe it is necessary to clarify pathogenic events not dependent on the accumulation of abnormal proteins (early-stage pathology). Post-mortem pathology specimens obtained from autopsies are extremely important for investigating the cause of disease but only allow for observations of neurodegeneration after it has occurred; therefore, most human specimens are unsuitable for analyses of disease onset or processes of neurodegeneration. Accordingly, we believe that it is important to use ‘disease models that can reproduce the exact state of the disease’.