{"doi":"10.1002/nep3.41","title":"Mitigating the impact of mechanisms causing neuronal degeneration","abstract":"Primary and secondary neurodegeneration is a pathological hallmark of numerous central nervous system (CNS) disorders. Although many mechanisms leading to neurodegeneration are well understood, previous approaches aiming at providing protection from neurodegeneration were often futile. A potential explanation may be that recent research discovered additional pathomechanisms leading to neurodegeneration. Thus, simply targeting single neurodegenerative mechanisms may only have minor therapeutic impact. Addressing multiple neurodegenerative mechanisms may be a more viable strategy. Moreover, the restoration of lost brain tissue turned out to be a very complex endeavor.1 Despite making some initial progress with the use of biocompatible scaffolds and hydrogels,2 the goal of meaningful restoration remains elusive so far. It is therefore essential to obtain a detailed and holistic understanding of neurodegenerative mechanisms to continuously improve our strategies to mitigate their impact in CNS disorders. This is particularly important for major diseases such as stroke, Alzheimer's disease, and vascular dementia, as they are leading contributors to severe disabilities, cognitive dysfunction, loss of quality of life, and patient mortality worldwide. This issue of Neuroprotection presents original contributions and reviews providing novel insights into mechanisms of primary and secondary neurodegeneration. Those may represent therapeutic targets for novel approaches to provide neuroprotection. This editorial highlights some intriguing aspects found within the articles published in the current issue of Neuroprotection. Haupt et al. review the role of microglia in ischemic stroke. As the resident CNS immune cells, microglia become activated after an ischemic event and contribute to pro-inflammatory signaling in early stages following stroke. They attract peripheral immune cells to the lesion site and facilitate ischemic lesion organization by removing cell debris. Microglia also exert anti-inflammatory functions, contributing to the resolution of neuroinflammation in subacute and chronic stages. However, microglia can contribute to secondary neuronal damage and cell loss when remaining in the pro-inflammatory activation state over extended time. Thus, a good balance between the pro-inflammatory and anti-inflammatory microglia polarization states is important for a good outcome after stroke. In their work, Haupt et al. explain microglia polarization including mixed phenotypes forming a spectrum in between the pro- and anti-inflammatory types. They also review in detail how microglia polarization can be beneficially modulated by stem cells and extracellular vesicles. Alzheimer's disease is among the most relevant neurodegenerative disorders. The often rapid decline in cognitive capabilities puts a significant burden to patients, their relatives and healthcare systems. Established treatments of Alzheimer's disease such as cholinesterase inhibitors, NMDA receptor antagonists and, more recently, monoclonal antibodies directed against the pathognomonic amyloid β plaques only have a minor therapeutic impact. The need for novel therapeutic approaches has therefore been a recurring topic in Neuroprotection.3, 4 Zhu et al. review the potential use of repetitive transcranial magnetic stimulation (rTMS) in Alzheimer's disease. The procedure is safe, noninvasive, and has been used in clinical trials on other CNS disorders including stroke. The authors start by providing a detailed overview of technical parameters of rTMS such as stimulus frequency, intensity, patterns, and coils. They also provide a thorough review of the clinical trials and report its impact on different brain areas such as the prefrontal cortex, the precuneus cortex, as well as on the cerebellum and explain novel rTMS application protocols. A major part of the review by Zhu et al. elucidates potential mechanisms of rTMS in Alzheimer's disease. They present evidence of neural netw","journal":"Neuroprotection/Neuroprotection (Chichester, England. Print)","year":2024,"id":490365,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":416236,"name":"Piotr Walczak","orcid":"0000-0002-3733-3322","position":1,"is_corresponding":false},{"id":851068,"name":"Johannes Boltze","orcid":"0000-0003-3956-4164","position":2,"is_corresponding":false},{"id":320471,"name":"Xunming Ji","orcid":"0000-0003-0293-2744","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-19T02:08:32.775003Z","pmid":"38645567","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}