The Alu neurodegeneration hypothesis: A primate-specific mechanism for neuronal transcription noise, mitochondrial dysfunction, and manifestation of neurodegenerative disease.

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2017-02-24

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Abstract

It is hypothesized that retrotransposons have played a fundamental role in primate evolution and that enhanced neurologic retrotransposon activity in humans may underlie the origin of higher cognitive function. As a potential consequence of this enhanced activity, it is likely that neurons are susceptible to deleterious retrotransposon pathways that can disrupt mitochondrial function. An example is observed in the TOMM40 gene, encoding a β-barrel protein critical for mitochondrial preprotein transport. Primate-specific Alu retrotransposons have repeatedly inserted into TOMM40 introns and at least one variant associated with late-onset Alzheimer's disease originated from an Alu insertion event. We provide evidence of enriched Alu content in mitochondrial genes and postulate that Alus can disrupt mitochondrial populations in neurons, thereby setting the stage for progressive neurologic dysfunction. This Alu neurodegeneration hypothesis is compatible with decades of research and offers a plausible mechanism for the disruption of neuronal mitochondrial homeostasis, ultimately cascading into neurodegenerative disease.

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10.1016/j.jalz.2017.01.017

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Larsen, PA, MW Lutz, KE Hunnicutt, M Mihovilovic, AM Saunders, AD Yoder and AD Roses (2017). The Alu neurodegeneration hypothesis: A primate-specific mechanism for neuronal transcription noise, mitochondrial dysfunction, and manifestation of neurodegenerative disease. Alzheimers Dement. 10.1016/j.jalz.2017.01.017 Retrieved from https://hdl.handle.net/10161/13815.

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Yoder

Anne Daphne Yoder

Braxton Craven Distinguished Professor of Evolutionary Biology

My work integrates field inventory activities with molecular phylogenetic techniques and geospatial analysis to investigate Madagascar, an area of the world that is biologically complex, poorly understood, and urgently threatened. Madagascar has been designated as one of the most critical geographic priorities for conservation action, retaining less than 10% of the natural habitats that existed before human colonization. It is critical that information be obtained as quickly as possible to document the biota that occurs in the remaining and highly threatened forested areas of western Madagascar, to gain an understanding of the evolutionary processes and associated distributional patterns that have shaped this diversity, and to use this information to help set conservation priorities. Phylogenetic and biogeographic analysis of Malagasy vertebrates, each with unique life-history and dispersal characteristics, are conducted to identify areas of high endemism potentially associated with underlying geological features, and also to test for the role that geographic features have played in generating patterns of vertebrate diversity and distribution. My lab also has a significant focus on capacity-building through the education and training of both American and Malagasy students. Research opportunities for American graduate students are enhanced by the formation of Malagasy/American partnerships.


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