α-synuclein (α-syn) is the main component of intracytoplasmic inclusions deposited in the brains of patients with Parkinson's disease (PD) and certain other neurodegenerative disorders. Recent studies have explored the ability of α-syn to propagate between or across neighboring neurons and supposedly "infect" them with a prion-like mechanism. However, much of this research has used stereotaxic injections of heterologous α-syn fibrils to induce the spreading of inclusions in the rodent brains. Whether α-syn is able to transmit from the host cells to their neighboring cells in vivo is unclear.

Voxel-based morphometry (VBM) using structural brain MRI has been widely used for the assessment of impairment in Alzheimer's disease (AD), but previous studies in VBM studies on AD remain inconsistent.

Language impairment is relatively common in Parkinson's disease (PD), but not all PD patients are susceptible to language problems. In this study, we identified among a sample of PD patients those pre-disposed to language impairment, describe their clinical profiles, and consider factors that may precipitate language disability in these patients.

Parkinson's Disease (PD) with mild cognitive impairment (MCI) (PD-MCI) represents one of the most dreaded complications for patients with PD and is associated with a higher risk of developing dementia. Although transcranial direct current stimulation (tDCS) has been demonstrated to improve motor and non-motor symptoms in PD, to date, no study has investigated the effects of tDCS on Theory of Mind (ToM), i.e., the ability to understand and predict other people's behaviours, in PD-MCI.

The administration of certain cannabinoids provides neuroprotection in models of neurodegenerative diseases by acting through various cellular and molecular mechanisms. Many cannabinoid actions in the nervous system are mediated by CB1 receptors, which can elicit psychotropic effects, but other targets devoid of psychotropic activity, including CB2 and nuclear PPARγ receptors, can also be the target of specific cannabinoids.

Alzheimer's disease (AD) is the most common form of dementia. At the present time, however, AD still lacks effective treatments. Our recent studies showed that chronic treatment with anesthetic propofol attenuated brain caspase-3 activation and improved cognitive function in aged mice. Accumulation of β-amyloid protein (Aβ) is a major component of the neuropathogenesis of AD dementia and cognitive impairment. We therefore set out to determine the effects of chronic treatment with propofol on Aβ levels in brain tissues of aged mice. Propofol (50 mg/kg) was administrated to aged (18 month-old) wild-type mice once a week for 8 weeks. The brain tissues of mice were harvested one day after the final propofol treatment. The harvested brain tissues were then subjected to enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Here we report that the propofol treatment reduced Aβ (Aβ40 and Aβ42) levels in the brain tissues of the aged mice. Moreover, the propofol treatment decreased the levels of β-site amyloid precursor protein cleaving enzyme (the enzyme for Aβ generation), and increased the levels of neprilysin (the enzyme for Aβ degradation) in the brain tissues of the aged mice. These results suggested that the chronic treatment with propofol might reduce brain Aβ levels potentially via decreasing brain levels of β-site amyloid precursor protein cleaving enzyme, thus decreasing Aβ generation; and via increasing brain neprilysin levels, thus increasing Aβ degradation. These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research.

Extensive loss of donor neural stem cell (NSCs) due to ischemic stress and low rate of differentiation at the site of cell graft are two of the major issues that hamper optimal outcome in NSCs transplantation studies. Given that histone deacetylases (HDACs) modulate various cellular processes by deacetylating histones and non-histone proteins, we hypothesized that combined treatment with small molecules, sodium butyrate (NaB; a known HDAC inhibitor) and nicorandil, will enhance the rate neuronal differentiation of NSCs besides their preconditioning to resist oxidative stress.

Curcumin,a natural polyphenol obtained from turmeric,has been implicated to be neuroprotective in a variety of neurodegenerative disorders although the mechanism remains poorly understood. The results of our recent experiments indicated that curcumin could protect dopaminergic neurons from apoptosis in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). The death of dopaminergic neurons and the loss of dopaminergic axon in the striatum were significantly suppressed by curcumin in MPTP mouse model. Further studies showed that curcumin inhibited JNKs hyperphosphorylation induced by MPTP treatment. JNKs phosphorylation can cause translocation of Bax to mitochondria and the release of cytochrome c which both ultimately contribute to mitochondria-mediated apoptosis. These pro-apoptosis effect can be diminished by curcumin. Our experiments demonstrated that curcumin can prevent nigrostriatal degeneration by inhibiting the dysfunction of mitochondrial through suppressing hyperphosphorylation of JNKs induced by MPTP. Our results suggested that JNKs/mitochondria pathway may be a novel target in the treatment of PD patients.

Diabetes is the most common metabolic disease with many chronic complications, and cognitive disorders are one of the common complications in patients with diabetes. Previous studies have showed that autophagy played important roles in the progression of metabolic syndrome, diabetes and other diseases. So we investigated whether aged diabetic mice are prone to be associated with the cognitive and affective disorders and whether Beclin-1-mediated autophagy might be involved in thepahological process.

CSF1R-related leukoencephalopathy, also known as hereditary diffuse leukoencephalopathy with spheroids (HDLS), is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown.

Early morning off (EMO) is a common feature of Parkinson's disease (PD). This study aimed to characterize its clinical features and develop a convenient and pragmatic self-assessment instrument in a Chinese nationwide population.

Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by dopaminergic nigrostriatal neuron loss and brain accumulation of Lewy bodies, protein aggregates mainly composed of α-synuclein. We reported that mice deficient for NF-κB/c-Rel (c-rel-/-) develop a late-onset parkinsonism. At 18 months of age, c-rel-/- mice showed nigrostriatal degeneration and accumulation of α-synuclein aggregates associated with a motor impairment responsive to L-DOPA administration. Being c-Rel protein a transcriptional regulator for mitochondrial anti-oxidant and antiapoptotic factors, it has been inferred that its deficiency may affect the resilience of "energy demanding" nigral dopaminergic neurons to the aging process. PD patients manifest a prodromal syndrome that includes olfactory and gastrointestinal dysfunctions years before the frank degeneration of nigrostriatal neurons and appearance of motor symptoms. According to the Braak staging, the onset of non-motor and motor symptoms relates to progressive ascendant diffusion of α-synuclein pathology in the brain. The aim of this study was to identify whether c-rel-/- deficiency is associated with the onset of premotor signs of PD and spatio-temporal progression of cerebral α-synuclein deposition.

In Alzheimer's Disease (AD), about one-third of the risk genes identified by GWAS encode proteins that function predominantly in the endocytic pathways. Among them, the Ras and Rab Interactor 3(RIN3) is a guanine nucleotide exchange factor (GEF) for the Rab5 small GTPase family and has been implicated to be a risk factor for both late onset AD (LOAD) and sporadic early onset AD (sEOAD). However, how RIN3 is linked to AD pathogenesis is currently undefined.

Alzheimer's disease is a neurodegenerative disorder. Therapeutically, a transplantation of bone marrow mesenchymal stem cells (BMMSCs) can play a beneficial role in animal models of Alzheimer's disease. However, the relevant mechanism remains to be fully elucidated.

Although many causative genes of hereditary spastic paraplegia (HSP) have been uncovered in recent years, there are still approximately 50% of HSP patients without genetically diagnosis, especially in autosomal recessive (AR) HSP patients. Rare studies have been performed to determine the genetic spectrum and clinical profiles of recessive HSP patients in the Chinese population.

Tai Chi has been shown to improve motor symptoms in Parkinson's disease (PD), but its long-term effects and the related mechanisms remain to be elucidated. In this study, we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms.

Interventional trials in amyotrophic lateral sclerosis (ALS) suffer from the heterogeneity of the disease as it considerably reduces statistical power. We asked if blood neurofilament light chains (NfL) could be used to anticipate disease progression and increase trial power.

Accumulating α-synuclein (α-syn) aggregates in neurons and glial cells are the staples of many synucleinopathy disorders, such as Parkinson's disease (PD). Since brain adenosine becomes greatly elevated in ageing brains and chronic adenosine A1 receptor (A1R) stimulation leads to neurodegeneration, we determined whether adenosine or A1R receptor ligands mimic the action of known compounds that promote α-syn aggregation (e.g., the amphetamine analogue 2-aminoindan) or inhibit α-syn aggregation (e.g., Rasagiline metabolite 1-aminoindan). In the present study, we determined whether adenosine, A1R receptor agonist N6-Cyclopentyladenosine (CPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) could directly interact with α-syn to modulate α-syn aggregation and neurodegeneration of dopaminergic neurons in the substantia nigra (SN).

Axons, crucial for impulse transmission and cellular trafficking, are thought to be primary targets of neurodegeneration in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Axonal degeneration occurs early, preceeding and exceeding neuronal loss, and contributes to the spread of pathology, yet is poorly described outside the nigrostriatal circuitry. The insula, a cortical brain hub, was recently discovered to be highly vulnerable to pathology and plays a role in cognitive deficits in PD and DLB. The aim of this study was to evaluate morphological features as well as burden of proteinopathy and axonal degeneration in the anterior insular sub-regions in PD, PD with dementia (PDD), and DLB.

Alzheimer's disease (AD) exhibits mitochondrial dysfunctions associated with dysregulated metabolism, brain inflammation, synaptic loss, and neuronal cell death. As a key protein serving as the mitochondrial gatekeeper, the voltage-dependent anion channel-1 (VDAC1) that controls metabolism and Ca2+ homeostasis is positioned at a convergence point for various cell survival and death signals. Here, we targeted VDAC1 with VBIT-4, a newly developed inhibitor of VDAC1 that prevents its pro-apoptotic activity, and mitochondria dysfunction.