The misfolding and aggregation of the largely disordered protein, α-synuclein, is a central pathogenic event that occurs in the synucleinopathies; a group of neurodegenerative disorders that includes Parkinson's disease.
This review examines experimental and clinical evidence relating to the potential role of SIRT1 and SIRT2, and their modulators in neurodegenerative diseases.
Misfolding and aggregate formation by the tau protein has been closely related with neurotoxicity in a large group of human neurodegenerative disorders, which includes Alzheimer's disease.
Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by abnormal expansion of glutamine (Q) encoding CAG repeats in the gene Ataxin-1 (ATXN1).
Synucleinopathies are neurodegenerative diseases characterized by the accumulation of either neuronal/axonal or glial insoluble proteinaceous aggregates mainly composed of α-synuclein (α-syn).
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra region and the presence of α-synuclein aggregates in the striatum and surrounding areas of brain.
Tauopathies such as Alzheimer's disease (AD), Pick's disease (PiD), Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) etc. represent a group of age-related neurodegenerative disorders in which tau protein loses its normal conformation mostly due to hyperphosphorylation and subsequent formation of the aggregates of defined shapes, known as Neurofibrillary Tangles (NFTs).
Understanding how Ataxin-1 expression is regulated in the human brain could inspire novel molecular therapies for this fatal, dominantly inherited neurodegenerative disease.
Cell-to-cell transmission of proteopathic alpha-synuclein (α-syn) seeds is increasingly thought to underlie the progression of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and related synucleinopathies.
Parkinson's disease (PD) is a serious neurodegenerative disease and is characterized by abnormal α-synuclein (α-syn) accumulation in Lewy bodies (LB) and Lewy neurites (LN), which makes α-syn an important imaging target for PD.
These data indicate that although aggregation of PAP and SNCA causes severe neurodegenerative diseases, PAP -/- with absence of the Snca does not appear to interrupt the cerebellar architecture development and zone and stripe pattern formation.
Aggregation of the amyloid-forming α-synuclein (αS) protein is closely associated with the etiology of Parkinson's disease (PD), the most common motor neurodegenerative disorder.
Tauopathies are a class of neurodegenerative diseases that are characterized by pathological aggregation of tau protein, which is accompanied by synaptic disorders.
These studies demonstrate that microglia cells are a new target cell of NGF in the brain and have therapeutic significance: i) they establish that the neuroprotective actions of hNGFp relies on a widespread exposure of the brain, ii) they identify a new anti-neurodegenerative pathway, linking hNGFp to inflammatory chemokines and cytokines via microglia, a common target for new therapeutic opportunities for neurodegenerative diseases, iii) they extend the neuroprotective potential of hNGFp beyond its classical cholinergic target, thereby widening the range of neurological diseases for which this neurotrophic factor might be used therapeutically, iv) they help interpreting the results of current NGF clinical trials in AD and the design of future trials with this new potent therapeutic candidate.
Several of these pyridine-fused rigid polyheterocycles are shown to bind to Aβ and α-synuclein fibrils, which are associated with neurodegenerative diseases.
Four-repeat (4R-) tauopathies are a group of neurodegenerative diseases defined by cytoplasmic inclusions predominantly composed of tau protein isoforms with four microtubule-binding domains.