The Latest Articles on Hallmarks of Neurodegenerative Diseases

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This week, we would like to share several latest articles on Hallmarks of Neurodegenerative Diseases.

Title: Hallmarks of neurodegenerative diseases

Authors: David M. Wilson III, Mark R. Cookson, Ludo Van Den Bosch, Henrik Zetterberg, David M. Holtzman, Ilse Dewachter

Type: Review

Abstract: 

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks of NDD: pathological protein aggregation, synaptic and neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA and RNA defects, inflammation, and neuronal cell death. We describe the hallmarks, their biomarkers, and their interactions as a framework to study NDDs using a holistic approach. The framework can serve as a basis for defining pathogenic mechanisms, categorizing different NDDs based on their primary hallmarks, stratifying patients within a specific NDD, and designing multi-targeted, personalized therapies to effectively halt NDDs.

Access this article: https://doi.org/10.1016/j.cell.2022.12.032

Title: lncRNA NEAT1: Key player in neurodegenerative diseases

Authors: Kun Li, Ziqiang Wang

Type: Review

Abstract:

Neurodegenerative diseases are the most common causes of disability worldwide. Given their high prevalence, devastating symptoms, and lack of definitive diagnostic tests, there is an urgent need to identify potential biomarkers and new therapeutic targets. Long non-coding RNAs (lncRNAs) have recently emerged as powerful regulatory molecules in neurodegenerative diseases. Among them, lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to be upregulated in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). However, whether this is part of a protective or harmful mechanism is still unclear. This review summarizes our current knowledge of the role of NEAT1 in neurodegenerative diseases and its association with the characteristic aggregation of misfolded proteins: amyloid-β and tau in AD, α-synuclein in PD, mutant huntingtin in HD, and TAR DNA-binding protein-43 fused in sarcoma/translocated in liposarcoma in ALS. The aim of this review is to stimulate further research on more precise and effective treatments for neurodegenerative diseases.

Access this article: https://doi.org/10.1016/j.arr.2023.101878

Title: Pathways to healing: Plants with therapeutic potential for neurodegenerative diseases

Authors: Sheena E.B. Tyler, Luke D.K. Tyler

Type: Research Article

Abstract:  

Some of the greatest challenges in medicine are the neurodegenerative diseases (NDs), which remain without a cure and mostly progress to death. A companion study employed a toolkit methodology to document 2001 plant species with ethnomedicinal uses for alleviating pathologies relevant to NDs, focusing on its relevance to Alzheimer’s disease (AD). This study aimed to find plants with therapeutic bioactivities for a range of NDs. 1339 of the 2001 plant species were found to have a bioactivity from the literature of therapeutic relevance to NDs such as Parkinson’s disease, Huntington’s disease, AD, motor neurone diseases, multiple sclerosis, prion diseases, Neimann-Pick disease, glaucoma, Friedreich's ataxia and Batten disease. 43 types of bioactivities were found, such as reducing protein misfolding, neuroinflammation, oxidative stress and cell death, and promoting neurogenesis, mitochondrial biogenesis, autophagy, longevity, and anti-microbial activity. Ethno-led plant selection was more effective than random selection of plant species. Our findings indicate that ethnomedicinal plants provide a large resource of ND therapeutic potential. The extensive range of bioactivities validate the usefulness of the toolkit methodology in the mining of this data. We found that a number of the documented plants are able to modulate molecular mechanisms underlying various key ND pathologies, revealing a promising and even profound capacity to halt and reverse the processes of neurodegeneration.

Access this article: https://doi.org/10.1016/j.ibneur.2023.01.006

Title: α-Synuclein Conformational Strains as Drivers of Phenotypic Heterogeneity in Neurodegenerative Diseases

Authors: Raphaella W.L. So, Joel C. Watts

Type: Review

Abstract:

The synucleinopathies, which include Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, are a class of human neurodegenerative disorders unified by the presence of α-synuclein aggregates in the brain. Considerable clinical and pathological heterogeneity exists within and among the individual synucleinopathies. A potential explanation for this variability is the existence of distinct conformational strains of α-synuclein aggregates that cause different disease manifestations. α-Synuclein strains can be delineated based on their structural architecture, with structural differences among α-synuclein aggregates leading to unique biochemical attributes and neuropathological properties in humans and animal models. Bolstered by recent high-resolution structural data from patient brain-derived material, it has now been firmly established that there are conformational differences among α-synuclein aggregates from different human synucleinopathies. Moreover, recombinant α-synuclein can be polymerized into several structurally distinct aggregates that exhibit unique pathological properties. In this review, we outline the evidence supporting the existence of α-synuclein strains and highlight how they can act as drivers of phenotypic heterogeneity in the human synucleinopathies.

Access this article: https://doi.org/10.1016/j.jmb.2023.168011

Title: Nicotinic acetylcholine receptors: Key targets for attenuating neurodegenerative diseases

Authors: Lydia J. Bye, Rocio K. Finol-Urdaneta, Han-Shen Tae, David J. Adams

Type: Review

Abstract:

Nicotinic acetylcholine receptors (nAChRs) are master regulators of immune functions via the cholinergic anti-inflammatory pathway and are expressed in microglia, the brain’s resident immune cells. There is an extensive dialogue between the neurons and the glial cells around them from which microglia are tasked with monitoring, nurturing, and defending their microenvironment. Dysregulation of any of these processes can have devastating and long-lasting consequences involving microglia-mediated neuroinflammation associated with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, amongst others. Disease-associated microglia acquire a distinguishing phenotype that emphasizes scavenging and defence functions while nurturing and repairing functions become muted. Attempts to resolve this critical imbalance remain a key focus of research. Furthermore, cholinergic modulation of neuroinflammation represents a promising avenue for treatment.

Access this article: https://doi.org/10.1016/j.biocel.2023.106387