{"doi":"10.1002/nep3.69","title":"Neurodegeneration in acute and chronic central nervous system disorders: Novel ideas and approaches","abstract":"Countering neurodegenerative processes remains a major obstacle, although we have witnessed significant recent progress in diagnostic and therapeutic approaches.1-3 The lack of true tissue regeneration is partially related to the absence of molecular, cellular, and anatomical cues in the adult mammalian central nervous system (CNS) that would allow for recapitulating ontogenesis and thus allow brain tissue regeneration.4 This drives the unabated need for better and earlier diagnosis as well as novel cytoprotective approaches in neurodegenerative disorders such as Alzheimer's disease (AD).5 Such approaches are covered in the current issue of Neuroprotection, which features a mixture of review papers as well as original articles and a clinical trial protocol. The main areas covered are AD and Parkinson's disease (PD), as well as ischemic CNS conditions. This editorial provides a summary of key findings and the most important conclusions reported in these articles. Blood-based biomarkers (BBMs) for AD are the primary focus of a review by Liu et al., who highlight the use of BBMs as a screening approach together with cognitive function assessments to select patients for subsequent diagnostic procedures such as lumbar puncture and advanced brain imaging. Although some of these BBMs may target unspecific processes related to AD pathophysiology (e.g., neurofilament light polypeptide to indicate neuronal injury), most of the available BBMs aim to detect pivotal AD pathomechanisms and hallmarks, including the plasma amyloid-beta (Aβ) 42/40 ratio or phosphorylated tau variants in the blood plasma. Further diagnostic precision can be achieved by considering specific genotypes6 such as apolipoprotein E4 expression. Liu et al. also focus on potential biomarkers currently under clinical assessment although those vary considerably regarding diagnostic accuracy. Importantly, the authors also focus on BBM limitations, such as a current lack of standardization regarding sampling, processing, and interpretation, particularly in the context of comorbidities. Multiomics approaches currently under development may provide future diagnostic improvements enabeling more precise and comprehensive AD diagnosis,7 ideally also in early or even prodromal stages. A review paper by Hanumanthappa et al. summarizes recent research in nanoparticles (NPs) as potential drug delivery systems to overcome the blood–brain barrier (BBB). This approach may be advantageous in numerous conditions, including AD and PD. The authors focus on surface-modified polymer NPs that exhibits better drug absorption and trans-BBB transport abilities. Next to a focus on NP composition and action, the review provides concise summaries of the BBB anatomy as well as of AD and PD pathomechanisms and established treatment options. This aids less experienced readers. The main part of this comprehensive review contains a detailed description of peptides and proteins used to functionalize NPs for enhanced trans-BBB transportation in AD or PD, respectively. The review also features a detailed overview of preclinical studies investigating the use of functionalized NPs, including a description of the drug load, route of administration, the disease model, and key experimental findings. The review concludes with a detailed description of three specific NP-based treatment concepts for AD and PD and a detailed outlook on potential future research directions. Thus, the work by Hanumanthappa et al. underlines the outstanding therapeutic potential of NPs for targeted AD and PD drug therapies. Khan et al. present a technologically interesting approach aiming at biomarker discovery for PD using mass spectrometry (MS) in a Drosophila melanogaster (DM) model system. These insect models only allow the investigation of genetic variants of PD, which are relatively rare in human PD patient populations. However, they allow a very focused and detailed investigation of the consequences of genetic mutations and the","journal":"Neuroprotection/Neuroprotection (Chichester, England. 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