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Biomedicines
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Novel Diagnostic and Therapeutic Strategy for Neurodegenerative Diseases
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Novel Diagnostic and Therapeutic Strategy for Neurodegenerative Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 3895

Special Issue Editor

Dr. Biyue Zhu

E-Mail Website
Guest Editor
Massachusetts General Hospital, Boston, MA 02114, USA
Interests: developing novel imaging probes; drug screening platforms; drug discovery for neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are characterized by the progressive death of neurons that cause neurological and neuropsychological symptoms, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), etc. Multiple factors of external environmental and internal genetic risk factors are related to these diseases. However, a clear mechanism is still elusive. The aggregation and propagation of a certain protein in the brain are the unique features of neurodegenerative diseases that cause downstream, harmful effects to neurons during disease progression. This feature occurs 10–20 years earlier before symptoms are observed; thus, early diagnosis methods are highly needed to facilitate the early diagnosis, etiology elucidation, and drug discovery of neurodegenerative disorders.

This Special Issue aims to understand the mechanisms and expand on the diagnostics and therapeutics required for neurodegenerative diseases. In particular, we will focus on understanding the molecular mechanisms of protein propagation, early diagnosis strategies, and imaging probe development, as well as drug screening, drug repurposing, and novel therapeutic strategies. We cordially invite authors and investigators within this complex field of universal interest to submit original research or review articles pertaining to this Special Issue.

Dr. Biyue Zhu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neurodegenerative disease
  • imaging probe
  • drug discovery
  • fluorescence imaging
  • chemiluminescence imaging
  • therapeutic strategy

Published Papers (3 papers)

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Research

22 pages, 7317 KiB  
Article
Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders
by Sadik Bay, Chander S. Digwal, Ananda M. Rodilla Martín, Sahil Sharma, Aleksandra Stanisavljevic, Anna Rodina, Anoosha Attaran, Tanaya Roychowdhury, Kamya Parikh, Eugene Toth, Palak Panchal, Eric Rosiek, Chiranjeevi Pasala, Ottavio Arancio, Paul E. Fraser, Melissa J. Alldred, Marco A. M. Prado, Stephen D. Ginsberg and Gabriela Chiosis
Biomedicines 2024, 12(6), 1252; https://doi.org/10.3390/biomedicines12061252 - 4 Jun 2024
Viewed by 940
Abstract
Neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce [...] Read more.
Neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce the synthesis and characterization of clickable epichaperome probes, PU-TCO, positive control, and PU-NTCO, negative control. Through comprehensive in vitro assays and cell-based investigations, we establish the specificity of the PU-TCO probe for epichaperomes. Furthermore, we demonstrate the efficacy of PU-TCO in detecting epichaperomes in brain tissue with a cellular resolution, underscoring its potential as a valuable tool for dissecting single-cell responses in neurodegenerative diseases. This clickable probe is therefore poised to address a critical need in the field, offering unprecedented precision and versatility in studying epichaperomes and opening avenues for novel insights into their role in disease pathology. Full article
(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Strategy for Neurodegenerative Diseases)
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19 pages, 7163 KiB  
Article
Accelerated Brain Atrophy, Microstructural Decline and Connectopathy in Age-Related Macular Degeneration
by Jacques A. Stout, Ali Mahzarnia, Rui Dai, Robert J. Anderson, Scott Cousins, Jie Zhuang, Eleonora M. Lad, Diane B. Whitaker, David J. Madden, Guy G. Potter, Heather E. Whitson and Alexandra Badea
Biomedicines 2024, 12(1), 147; https://doi.org/10.3390/biomedicines12010147 - 10 Jan 2024
Cited by 2 | Viewed by 1138
Abstract
Age-related macular degeneration (AMD) has recently been linked to cognitive impairment. We hypothesized that AMD modifies the brain aging trajectory, and we conducted a longitudinal diffusion MRI study on 40 participants (20 with AMD and 20 controls) to reveal the location, extent, and [...] Read more.
Age-related macular degeneration (AMD) has recently been linked to cognitive impairment. We hypothesized that AMD modifies the brain aging trajectory, and we conducted a longitudinal diffusion MRI study on 40 participants (20 with AMD and 20 controls) to reveal the location, extent, and dynamics of AMD-related brain changes. Voxel-based analyses at the first visit identified reduced volume in AMD participants in the cuneate gyrus, associated with vision, and the temporal and bilateral cingulate gyrus, linked to higher cognition and memory. The second visit occurred 2 years after the first and revealed that AMD participants had reduced cingulate and superior frontal gyrus volumes, as well as lower fractional anisotropy (FA) for the bilateral occipital lobe, including the visual and the superior frontal cortex. We detected faster rates of volume and FA reduction in AMD participants in the left temporal cortex. We identified inter-lingual and lingual–cerebellar connections as important differentiators in AMD participants. Bundle analyses revealed that the lingual gyrus had a lower streamline length in the AMD participants at the first visit, indicating a connection between retinal and brain health. FA differences in select inter-lingual and lingual cerebellar bundles at the second visit showed downstream effects of vision loss. Our analyses revealed widespread changes in AMD participants, beyond brain networks directly involved in vision processing. Full article
(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Strategy for Neurodegenerative Diseases)
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17 pages, 3622 KiB  
Article
Development of 2′-O-Methyl and LNA Antisense Oligonucleotides for SMN2 Splicing Correction in SMA Cells
by Marianna Maretina, Arina Il’ina, Anna Egorova, Andrey Glotov and Anton Kiselev
Biomedicines 2023, 11(11), 3071; https://doi.org/10.3390/biomedicines11113071 - 16 Nov 2023
Viewed by 1353
Abstract
Spinal muscular atrophy (SMA) is a devastating neurodegenerative disease caused by mutations in the SMN1 gene. Existing therapies demonstrate positive results on SMA patients but still might be ameliorated in efficacy and price. In the presented study we designed antisense oligonucleotides (AONs), targeting [...] Read more.
Spinal muscular atrophy (SMA) is a devastating neurodegenerative disease caused by mutations in the SMN1 gene. Existing therapies demonstrate positive results on SMA patients but still might be ameliorated in efficacy and price. In the presented study we designed antisense oligonucleotides (AONs), targeting intronic splicing silencer sites, some were modified with 2′-O-methyl, others with LNA. The AONs have been extensively tested in different concentrations, both individually and combined, in order to effectively target the ISS-N1 and A+100G splicing silencer regions in intron 7 of the SMN2 gene. By treating SMA-cultured fibroblasts with certain AONs, we discovered a remarkable increase in the levels of full-length SMN transcripts and the number of nuclear gems. This increase was observed to be dose-dependent and reached levels comparable to those found in healthy cells. When added to cells together, most of the tested molecules showed a remarkable synergistic effect in correcting splicing. Through our research, we have discovered that the impact of oligonucleotides is greatly influenced by their length, sequence, and pattern of modification. Full article
(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Strategy for Neurodegenerative Diseases)
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