Abstract：
:A hallmark event in neurodegenerative diseases (NDs) is the misfolding, aggregation, and accumulation of proteins, leading to cellular dysfunction, loss of synaptic connections, and brain damage. Despite the involvement of distinct proteins in different NDs, the process of protein misfolding and aggregation is remarkably similar. A recent breakthrough in the field was the discovery that misfolded protein aggregates can self-propagate through seeding and spread the pathological abnormalities between cells and tissues in a manner akin to the behavior of infectious prions in prion diseases. This discovery has vast implications for understanding the mechanisms involved in the initiation and progression of NDs, as well as for the design of novel strategies for treatment and diagnosis. In this Review, we provide a critical discussion of the role of protein misfolding and aggregation in NDs. Commonalities and differences between distinct protein aggregates will be highlighted, in addition to evidence supporting the hypothesis that misfolded aggregates can be transmissible by the prion principle. We will also describe the molecular basis and implications for prion-like conformational strains, cross-interaction between different misfolded proteins in the brain, and how these concepts can be applied to the development of novel strategies for therapy and diagnosis.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Soto C,Pritzkow Sdoi
10.1038/s41593-018-0235-9subject
Has Abstractpub_date
2018-10-01 00:00:00pages
1332-1340issue
10eissn
1097-6256issn
1546-1726pii
10.1038/s41593-018-0235-9journal_volume
21pub_type
杂志文章,评审abstract：:Grid cells in layer II of the medial entorhinal cortex form a principal component of the mammalian neural representation of space. The firing pattern of a single grid cell has been hypothesized to be generated through attractor dynamics in a network with a specific local connectivity including both excitatory and inhi...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3310
更新日期：2013-03-01 00:00:00
abstract：:Learning and memory are associated with the formation and modification of neuronal assemblies: populations of neurons that encode what has been learned and mediate memory retrieval upon recall. Functional studies of neuronal assemblies have progressed dramatically thanks to recent technological advances. Here we discu...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.4418
更新日期：2016-12-01 00:00:00
abstract：:To determine the number of open Ca(2+) channels necessary for transmitter release at the inhibitory basket cell-granule cell synapse in rat hippocampus, we combined presynaptic Ca(2+) imaging, recording of postsynaptic currents and modeling. We found that that the opening of three or fewer Ca(2+) channels triggered tr...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2461
更新日期：2010-01-01 00:00:00
abstract：:Recent evidence suggests that presynaptic-acting NMDA receptors (preNMDARs) are important for neocortical synaptic transmission and plasticity. We found that unique properties of the NR3A subunit enable preNMDARs to enhance spontaneous and evoked glutamate release and that NR3A is required for spike timing-dependent l...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2750
更新日期：2011-03-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature neuroscience
pub_type： 已发布勘误
doi：10.1038/s41593-019-0570-5
更新日期：2020-02-01 00:00:00
abstract：:Distinct cell lineages established early in development are usually maintained throughout adulthood. Thus, adult stem cells have been thought to generate differentiated cells specific to the tissue in which they reside. This view has been challenged; for example, neural stem cells can generate cells that normally orig...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/79924
更新日期：2000-10-01 00:00:00
abstract：:The retina of warm-blooded vertebrates is believed to be incapable of neural regeneration. Here we provide evidence that the retina of postnatal chickens has the potential to generate new neurons. In response to acute damage, numerous Müller glia re-entered the cell cycle, and shortly thereafter, expressed CASH-1, Pax...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/85090
更新日期：2001-03-01 00:00:00
abstract：:Microglia are primary immune sentinels of the CNS. Following injury, these cells migrate or extend processes toward sites of tissue damage. CNS injury is accompanied by release of nucleotides, serving as signals for microglial activation or chemotaxis. Microglia express several purinoceptors, including a G(i)-coupled ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1805
更新日期：2006-12-01 00:00:00
abstract：:The origin of brain mechanisms that support human language-whether these originated de novo in humans or evolved from a neural substrate that existed in a common ancestor-remains a controversial issue. Although the answer is not provided by the fossil record, it is possible to make inferences by studying living specie...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1741
更新日期：2006-08-01 00:00:00
abstract：:Timing is crucial to many aspects of human performance. To better understand its neural underpinnings, we used event-related fMRI to examine the time course of activation associated with different components of a time perception task. We distinguished systems associated with encoding time intervals from those related ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/85191
更新日期：2001-03-01 00:00:00
abstract：:It is often assumed that all neurons of the same cell type have identical intrinsic properties, both within an animal and between animals. We exploited the large size and small number of unambiguously identifiable neurons in the crab stomatogastric ganglion to test this assumption at the level of channel mRNA expressi...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1639
更新日期：2006-03-01 00:00:00
abstract：:The projections and odor responses of mammalian olfactory receptor neurons, as well as the physiology of the bulb's principal neurons-the mitral cells (MCs)-are known from studies in slices and anesthetized animals. In behaving rats trained to discriminate between two odors associated with different reinforcers, we ex...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/14801
更新日期：1999-11-01 00:00:00
abstract：:The production of hippocampal granule neurons continues throughout adulthood but dramatically decreases in old age. Here we show that reducing corticosteroid levels in aged rats restored the rate of cell proliferation, resulting in increased numbers of new granule neurons. This result indicates that the neuronal precu...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/13197
更新日期：1999-10-01 00:00:00
abstract：:Dopamine signaling is implicated in reinforcement learning, but the neural substrates targeted by dopamine are poorly understood. We bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1 or D2 receptor–expressing striatal projection neurons influenced reinforcement learning in mice. S...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3100
更新日期：2012-06-01 00:00:00
abstract：:We demonstrate a form of long-term depression (LTD) in the perirhinal cortex that relies on interaction between different glutamate receptors. Group II metabotropic glutamate (mGlu) receptors facilitated group I mGlu receptor-mediated increases in intracellular calcium. This facilitation plus NMDA receptor activation ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/72093
更新日期：2000-02-01 00:00:00
abstract：:We used fluorescent in-situ hybridization and confocal microscopy to monitor the subcellular distribution of the immediate-early gene Arc. Arc RNA appeared in discrete intranuclear foci within minutes of neuronal activation and subsequently disappeared from the nucleus and accumulated in the cytoplasm by 30 minutes. T...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/16046
更新日期：1999-12-01 00:00:00
abstract：:Animals strategically scan the environment to form an accurate perception of their surroundings. Here we investigated the neuronal representations that mediate this behavior. Ca2+ imaging and selective optogenetic manipulation during an active sensing task reveals that layer 5 pyramidal neurons in the vibrissae cortex...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0254-6
更新日期：2018-11-01 00:00:00
abstract：:Over the last 10 years, optogenetics has become widespread in neuroscience for the study of how specific cell types contribute to brain functions and brain disorder states. The full impact of optogenetics will emerge only when other toolsets mature, including neural connectivity and cell phenotyping tools and neural r...
journal_title：Nature neuroscience
pub_type： 评论,杂志文章
doi：10.1038/nn.4094
更新日期：2015-09-01 00:00:00
abstract：:Cognition can be conceptualized as a set of algorithmic control functions whose real-time deployment determines how an organism stores and uses information to guide thought and action. A subset of these functions is required for goal-directed selection and amplification of sensory signals-broadly referred to as attent...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/s41593-017-0020-1
更新日期：2017-12-01 00:00:00
abstract：:Here, we characterized behavioral abnormalities induced by prolonged social isolation in adult rodents. Social isolation induced both anxiety- and anhedonia-like symptoms and decreased cAMP response element-binding protein (CREB) activity in the nucleus accumbens shell (NAcSh). All of these abnormalities were reversed...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2257
更新日期：2009-02-01 00:00:00
abstract：:The structure and function of presynaptic and postsynaptic compartments varies markedly in neurons, but little is known about how they are functionally arranged with respect to each other. In rat hippocampal neurons, we found that, although they are structurally correlated from the early moments of formation, synapses...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2826
更新日期：2011-06-01 00:00:00
abstract：:Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog LeuT. Our models suggest ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2146
更新日期：2008-07-01 00:00:00
abstract：:To discover novel genes underlying amyotrophic lateral sclerosis (ALS), we aggregated exomes from 3,864 cases and 7,839 ancestry-matched controls. We observed a significant excess of rare protein-truncating variants among ALS cases, and these variants were concentrated in constrained genes. Through gene level analyses...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-019-0530-0
更新日期：2019-12-01 00:00:00
abstract：:Though motor neurons selectively degenerate in amyotrophic lateral sclerosis, other cell types are likely involved in this disease. We recently generated rNLS8 mice in which human TDP-43 (hTDP-43) pathology could be reversibly induced in neurons and expected that microglia would contribute to neurodegeneration. Howeve...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0083-7
更新日期：2018-03-01 00:00:00
abstract：:Imaging, from magnetic resonance imaging (MRI) to localization of specific macromolecules by microscopies, has been one of the driving forces behind neuroinformatics efforts of the past decade. Many web-accessible resources have been created, ranging from simple data collections to highly structured databases. Althoug...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1229
更新日期：2004-05-01 00:00:00
abstract：:Neural activity in visual area V4 is enhanced when attention is directed into neuronal receptive fields. However, the source of this enhancement is unclear, as most physiological studies have manipulated attention by changing the absolute reward associated with a particular location as well as its value relative to ot...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4141
更新日期：2015-11-01 00:00:00
abstract：:Previous gene knockout studies have shown that the orphan glutamate receptor delta2 (GluRdelta2) is critically involved in synaptogenesis between parallel fibers and Purkinje cells during development. However, the precise function of GluRdelta2 and whether it is functional in the mature cerebellum remain unclear. To a...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1086
更新日期：2003-08-01 00:00:00
abstract：:We report a systematic relationship between sound-frequency tuning and sensitivity to interaural time delays for neurons in the midbrain nucleus of the inferior colliculus; neurons with relatively low best frequencies (BFs) showed response peaks at long delays, whereas neurons with relatively high BFs showed response ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/86049
更新日期：2001-04-01 00:00:00
abstract：:Persistent neural activity in the absence of a stimulus has been identified as a neural correlate of working memory, but how such activity is maintained by neocortical circuits remains unknown. We used a computational approach to show that the inhibitory and excitatory microcircuitry of neocortical memory-storing regi...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3492
更新日期：2013-09-01 00:00:00
abstract：:Speech and vocal impairments characterize many neurological disorders. However, the neurogenetic mechanisms of these disorders are not well understood, and current animal models do not have the necessary circuitry to recapitulate vocal learning deficits. We developed germline transgenic songbirds, zebra finches (Tanei...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4133
更新日期：2015-11-01 00:00:00
