Tauopathies encompass a group of approximately 20 neurodegenerative diseases characterized by the accumulation of the microtubule-associated protein tau in brain neurons. The pathogenesis of intracellular neurofibrillary tangles, a hallmark of tauopathies, is initiated by hyperphosphorylated tau protein isoforms that cause neuronal death and lead to diseases like Alzheimer's, Parkinson's disease, frontotemporal dementia, and other complex neurodegenerative diseases. Current applications of tau biomarkers, including imaging, cerebrospinal fluid, and blood-based assays, assist in the evaluation and diagnosis of tauopathies. Emerging research is providing various potential strategies to prevent cellular toxicity caused by tau aggregation such as: 1) suppressing toxic tau aggregation, 2) preventing post-translational modifications of tau, 3) stabilizing microtubules and 4) designing tau-directed immunogens. This review aims to discuss the role of tau in tauopathies along with neuropathological features of the different tauopathies and the new developments in treating tau aggregation with the therapeutics for treating and possibly preventing tauopathies.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arr.2024.102639DOI Listing

Publication Analysis

Top Keywords

tau aggregation
12
neurodegenerative diseases
8
tau
8
tauopathies
6
targeting tau
4
tau alzheimer's
4
alzheimer's insights
4
insights pathology
4
pathology therapeutic
4
therapeutic strategies
4

Similar Publications

Rare genetic disorders are low in prevalence and hence there is little or no attention paid to them in the mainstream medical industry. One of the ultra-rare neuromuscular disorders, GNE myopathy is caused due to biallelic mutations in the bifunctional enzyme, GNE (UDP N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase). It catalyses the rate-limiting step in sialic acid biosynthesis.

View Article and Find Full Text PDF

Background: Spinocerebellar ataxias (SCAs) encompass a wide spectrum of inherited neurodegenerative diseases, primarily characterized by pathological changes in the cerebellum, spinal cord, and brainstem degeneration. Autosomal dominant spinocerebellar ataxia type 48 (SCA48) is a newly identified subtype of SCA, marked by early-onset ataxia and cognitive impairment, and is associated with mutations in the STIP1 homology and U-box-containing protein 1 (STUB1) gene. The STUB1 gene encodes the protein CHIP (C-terminus of HSC70-interacting protein) which functions as E3 ubiquitin ligase and is crucial to the development of neural systems.

View Article and Find Full Text PDF

Neurodegeneration refers to the gradual loss of neurons and extensive changes in glial cells like tau inclusions in astrocytes and oligodendrocytes, α-synuclein inclusions in oligodendrocytes and SOD1 aggregates in astrocytes along with deterioration in the motor, cognition, learning, and behavior. Common neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), spinocerebellar ataxia (SCA), and supranuclear palsy. There is a lack of effective treatment for neurodegenerative diseases, and scientists are putting their efforts into developing therapies against them.

View Article and Find Full Text PDF

Biomarkers of Synaptic Degeneration in Alzheimer's Disease.

Ageing Res Rev

December 2024

Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China; Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China. Electronic address:

Synapse has been considered a critical neuronal structure in the procession of Alzheimer's disease (AD), attacked by two pathological molecule aggregates (amyloid-β and phosphorylated tau) in the brain, disturbing synaptic homeostasis before disease manifestation and subsequently causing synaptic degeneration. Recently, evidence has emerged indicating that soluble oligomeric amyloid-β (AβO) and tau exert direct toxicity on synapses, causing synaptic damage. Synaptic degeneration is closely linked to cognitive decline in AD, even in the asymptomatic stages of AD.

View Article and Find Full Text PDF

Neprilysin (NEP) is a neutral endopeptidase, important for the degradation of amyloid beta (Aβ) peptides and other neuropeptides, including enkephalins, substance P, and bradykinin, in the brain, that influences various physiological processes such as blood pressure homeostasis, pain perception, and neuroinflammation. NEP breaks down Aβ peptides into smaller fragments, preventing the development of detrimental aggregates such as Aβ plaques. NEP clears Aβ plaques predominantly by enzymatic breakdown in the extracellular space.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!