{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:03:45Z","timestamp":1792623825491,"version":"4.5.0"},"reference-count":83,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:p>Background: Loss of Cholinergic Receptor Muscarinic 1 (CHRM1) has been linked to the pathogenesis of Alzheimer\u2019s disease (AD). Our recent study found significantly lower CHRM1 protein levels in AD patient cortices, linked to reduced survival. Furthermore, using knockout mice (Chrm1\u2212\/\u2212) we demonstrated that deletion of Chrm1 alters cortical mitochondrial structure and function, directly establishing a connection between its loss and mitochondrial dysfunction in the context of AD. While CHRM1\u2019s role in the brain has been extensively investigated, its impact on peripheral neurons in AD remains a crucial area of research, especially considering reported declines in peripheral nerve conduction among AD patients. Objective: The objective was to characterize Chrm1 localization and mitochondrial deficits in Chrm1\u2212\/\u2212 dorsal root ganglion (DRG) neurons. Methods: Recombinant proteins tagged with Green or Red Fluorescent Protein (GFP\/RFP) were transiently expressed to investigate the localization of Chrm1 and mitochondria, as well as mitochondrial movement in the neurites of cultured primary mouse DRG neurons, using confocal time-lapse live cell imaging. Transmission electron microscopy was performed to examine the ultrastructure of mitochondria in both wild-type and Chrm1\u2212\/\u2212 DRGs. Results: Fluorescence imaging revealed colocalization and comigration of N-terminal GFP-tagged Chrm1 and mitochondrial localization signal peptide-tagged RFP-labelled mitochondria in the DRGs neurons. A spectrum of mitochondrial structural abnormalities, including disruption and loss of cristae was observed in 87% neurons in Chrm1\u2212\/\u2212 DRGs. Conclusions: This study suggests that Chrm1 may be localized in the neuronal mitochondria and loss of Chrm1 in peripheral neurons causes sever mitochondrial structural aberrations resembling AD pathology.<\/jats:p>","DOI":"10.3233\/jad-230883","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T10:58:01Z","timestamp":1709031481000},"page":"247-264","source":"Crossref","is-referenced-by-count":3,"title":["Cholinergic Receptor Muscarinic 1 Co-Localized with Mitochondria in Cultured Dorsal Root Ganglion Neurons, and Its Deletion Disrupted Mitochondrial Ultrastructure in Peripheral Neurons: Implications in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"98","author":[{"given":"Mohammad Golam","family":"Sabbir","sequence":"first","affiliation":[{"name":"Department of Psychology and Neuroscience, Collegeof Psychology, Nova Southeastern University, Fort Lauderdale, FL, USA"},{"name":"Alzo Biosciences Inc., San Diego, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-230883_ref1","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.3390\/molecules27061816","article-title":"Role of cholinergic signaling in Alzheimer\u2019s disease","volume":"27","author":"Chen","year":"2022","journal-title":"Molecules"},{"key":"10.3233\/JAD-230883_ref2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fnmol.2019.00204","article-title":"New insights into cholinergic neuron diversity","volume":"12","author":"Ahmed","year":"2019","journal-title":"Front Mol Neurosci"},{"key":"10.3233\/JAD-230883_ref3","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1093\/brain\/awv024","article-title":"Neuronal amyloid-\u03b2accumulation within cholinergic basal forebrain in ageing and Alzheimer\u2019s disease","volume":"138","author":"Baker-Nigh","year":"2015","journal-title":"Brain"},{"key":"10.3233\/JAD-230883_ref4","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer\u2019s disease","volume":"141","author":"Hampel","year":"2018","journal-title":"Brain"},{"key":"10.3233\/JAD-230883_ref5","doi-asserted-by":"crossref","first-page":"fcaa058","DOI":"10.1093\/braincomms\/fcaa058","article-title":"M1 muscarinic acetylcholine receptor dysfunction in moderate Alzheimer\u2019s disease pathology","volume":"2","author":"Yi","year":"2020","journal-title":"Brain Commun"},{"key":"10.3233\/JAD-230883_ref6","doi-asserted-by":"crossref","first-page":"6753","DOI":"10.1073\/pnas.93.13.6753","article-title":"Amyloid beta-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons","volume":"93","author":"Kelly","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-230883_ref7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.mcn.2007.12.010","article-title":"Extracellular tau promotes intracellular calcium increase through M1 and M3 muscarinic receptors in neuronal cells","volume":"37","author":"G\u00f3mez-Ramos","year":"2008","journal-title":"Mol Cell Neurosci"},{"key":"10.3233\/JAD-230883_ref8","first-page":"427","article-title":"Interactions between beta-amyloid and central cholinergic neurons: Implications for Alzheimer\u2019s disease","volume":"29","author":"Kar","year":"2004","journal-title":"J Psychiatry Neurosci"},{"key":"10.3233\/JAD-230883_ref9","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1074\/jbc.272.4.2038","article-title":"Nontoxic amyloid beta peptide 1\u201342 suppresses acetylcholine synthesis. 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