{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T15:25:31Z","timestamp":1776525931013,"version":"3.51.2"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006280","name":"Ministerio de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["SAF2016-78892R"],"award-info":[{"award-number":["SAF2016-78892R"]}],"id":[{"id":"10.13039\/501100006280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["766124"],"award-info":[{"award-number":["766124"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Synaptic disruption and altered neurotransmitter release occurs in the brains of patients and in murine models of neurodegenerative diseases (NDDs). During the last few years, evidence has accumulated suggesting that the sympathoadrenal axis is also affected as disease progresses. Here, we review a few studies done in adrenal medullary chromaffin cells (CCs), that are considered as the amplifying arm of the sympathetic nervous system; the sudden fast exocytotic release of their catecholamines\u2014stored in noradrenergic and adrenergic cells\u2014plays a fundamental role in the stress fight-or-flight response. Bulk exocytosis and the fine kinetics of single-vesicle exocytotic events have been studied in mouse models carrying a mutation linked to NDDs. For instance, in R6\/1 mouse models of Huntington\u2019s disease (HD), mutated huntingtin is overexpressed in CCs; this causes decreased quantal secretion, smaller quantal size and faster kinetics of the exocytotic fusion pore, pore expansion, and closure. This was accompanied by decreased sodium current, decreased acetylcholine-evoked action potentials, and attenuated [Ca2+]c transients with faster Ca2+ clearance. In the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS), CCs exhibited secretory single-vesicle spikes with a slower release rate but higher exocytosis. Finally, in the APP\/PS1 mouse model of Alzheimer\u2019s disease (AD), the stabilization, expansion, and closure of the fusion pore was faster, but the secretion was attenuated. Additionally, \u03b1-synuclein that is associated with Parkinson\u2019s disease (PD) decreases exocytosis and promotes fusion pore dilation in adrenal CCs. Furthermore, Huntington-associated protein 1 (HAP1) interacts with the huntingtin that, when mutated, causes Huntington\u2019s disease (HD); HAP1 reduces full fusion exocytosis by affecting vesicle docking and controlling fusion pore stabilization. The alterations described here are consistent with the hypothesis that central alterations undergone in various NDDs are also manifested at the peripheral sympathoadrenal axis to impair the stress fight-or-flight response in patients suffering from those diseases. Such alterations may occur: (i) primarily by the expression of mutated disease proteins in CCs; (ii) secondarily to stress adaptation imposed by disease progression and the limitations of patient autonomy.<\/jats:p>","DOI":"10.3390\/ijms21061946","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T12:22:51Z","timestamp":1584015771000},"page":"1946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Disruption of Exocytosis in Sympathoadrenal Chromaffin Cells from Mouse Models of Neurodegenerative Diseases"],"prefix":"10.3390","volume":"21","author":[{"given":"Antonio M. G.","family":"de Diego","sequence":"first","affiliation":[{"name":"Instituto Te\u00f3filo Hernando, Departamento. de Farmacolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Ortega-Cruz","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando, Departamento. de Farmacolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio G.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando, Departamento. de Farmacolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/jnc.14723","article-title":"Alterations in synaptic function and plasticity in Huntington disease","volume":"150","author":"Sepers","year":"2019","journal-title":"J. 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