Bridging the gap: large animal models in neurodegenerative research

摘要: The world health organisation has declared neurological disorders as one of the greatest public risks in today. Yet, despite this growing concern, mechanisms underpinning many these conditions are still poorly understood. This may part be due to seemingly diverse nature initiating insults ranging from genetic (such Ataxia’s and Lysosomal storage disorders) through protein misfolding aggregation (i.e. Prions), those a predominantly unknown aetiology Alzheimer’s Parkinson’s disease). However, efforts elucidate mechanistic regulation also likely hampered because complexity human nervous system, apparent selective regional vulnerability differential degenerative progression. key elucidating aetiologies is determining molecular cascades, which occurring early terminal stages disease Whilst much data have been captured at end stage post-mortem analysis humans, very often conspicuously asymptomatic, even if they were not, repeated sampling multiple brain regions “affected” patients “controls” neither ethical nor possible. Model systems therefore become fundamental for governing complex neurodegenerative conditions. finding model that precisely mimics condition can challenging expensive. cellular invertebrate models frequently used research undoubtedly yielded useful data, comparatively simplistic makes insights gained such stand alone limited when it comes translation. Given recent advances gene editing technology, options novel generation higher order species opened up new exciting possibilities field. In review, we explain some reasons why larger animal appear give more robust recapitulation critical stepping stone effective therapeutic