Senescence is a biological process that causes a progressive deterioration of structure and function of all organs chronologically. Recent studies have revealed the detailed molecular mechanisms of senescence using cell culture system and experimental organisms. It is thought that senescence is a potential cause for the development of various age-related disorders such as cancer, cardiovascular and neurodegenerative disorders.
Neurodegenerative disorders are common and devastating. Rationally, the most
effective treatments will target pathogenetic mechanisms. While alternative approaches,
based on alleviating the symptoms of patients with Alzheimer disease,
Parkinson disease, Huntington disease, prion disorders or amyotrophic lateral sclerosis,
can be expected to reduce suffering, studies of pathogenesis of these agerelated
disorderswill be most important for enabling early diagnosis and the creation
of preventative and curative treatments.
Among all the clinical indications for which radiologists, nuclear medicine physicians,
neurologists, neurosurgeons, psychiatrists (and others examining disorders of
the brain) order and read brain PET scans, demand is greatest for those pertaining
to dementia and related disorders. This demand is driven by the sheer prevalence of
those conditions, coupled with the fact that the differential diagnosis for causes of
cognitive impairment is wide and often difficult to distinguish clinically.
Parkinsonism and Freezing Gait
Parkinson's disease (Chap. 366) is common, affecting 1% of the population 55. The stooped posture and shuffling gait are characteristic and distinctive features. Patients sometimes accelerate (festinate) with walking or display retropulsion. There may be difficulty with gait initiation (freezing) and a tendency to turn en bloc. Imbalance and falls may develop as the disease progresses over years.
Proteins are occasionally converted from their normal soluble state to
highly ordered fibrillar aggregates (amyloids), which give rise to pathologi-cal conditions that range from neurodegenerative disorders to systemic
amyloidoses. Recent methodological advances in solid-state NMR and
EPR spectroscopy have enabled determination of the 3D structure of sev-eral amyloids at residue-level resolution.
Neurodegenerative disorders, such as Huntington’s, Alzheimer’s, and
Parkinson’s diseases, affect millions of people worldwide and currently there
are few effective treatments and no cures for these diseases. Transgenic mice
expressing human transgenes for huntingtin, amyloid precursor protein, and
other genes associated with familial forms of neurodegenerative disease in
humans provide remarkable tools for studying neurodegeneration because
they mimic many of the pathological and behavioural features of the human
Representing one of the most important lifestyle factors, diet can strongly influence
the incidence and onset of cardiovascular disease and neurodegenerative disorders.
Recent dietary intervention studies in several mammalian species, including humans,
with flavonoid-rich foods, in particular Vitis vinifera (grape), Camellia sinensis (tea),
Theobroma cacao (cocoa), and Vaccinium spp. (blueberry), have indicated an ability
of these dietary components to improve memory and learning.
Population Screening Mass genetic screening programs require tests of high enough sensitivity and specificity to be cost-effective. An effective screening program should fulfill the following criteria: that the tested disorder is prevalent and serious; that it can be influenced presymptomatically through lifestyle changes, screening, or medications; and that identification of risk does not result in undue discrimination or harm.
Other Diseases The power and versatility of gene transfer approaches are such that there are few serious disease entities for which gene transfer therapies are not under development. Besides those already discussed, other areas of interest include gene therapies for HIV and for neurodegenerative disorders.
Brain morphology is in constant change from the very beginning of the neurodevelopment in human beings. The characterization of the brain morphology and its biological implications on a specific subject is a complex task which requires efficient computational approaches. Radiology has traditionally assessed the main brain changes in different alterations from a macroscopic point of view, thus, not considering subtle changes as a results of neuronal plasticity.
Neurodegenerative disorders are associated with oxidative stress. Low den-sity lipoprotein (LDL) exists in the brain and is especially sensitive to oxi-dative damage. Oxidative modification of LDL has been implicated in
the pathogenesis of neurodegenerative diseases. Therefore, protecting LDL
from oxidation may be essential in the brain.
A large number of neurodegenerative diseases in humans result from pro-tein misfolding and aggregation. Protein misfolding is believed to be the
primary cause of Alzheimer’s disease, Parkinson’s disease, Huntington’s
disease, Creutzfeldt–Jakob disease, cystic fibrosis, Gaucher’s disease and
many other degenerative and neurodegenerative disorders.
Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two
Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by cortico-striatal dysfunction and loss of glutamate uptake. At 7 weeks of age, R6/2 mice, which model an aggressive form of juvenile HD, show a glutamate-uptake deficit in striatum that can be reversed by treatment with ceftriaxone, a b-lactam antibiotic that increases GLT1 expression. Only at advanced ages ( 11 weeks), however, do R6/2 mice show an actual loss of striatal GLT1. Here, we tested whether ceftriaxone can reverse the decline in GLT1 expression that occurs in older R6/2s.
Parkinson’s disease is the second most common neurodegenerative disorder. The pathological hallmark of the disease is degeneration of midbrain dopaminergic neurons. Genetic association studies have linked 13 human chromosomal loci to Parkinson’s disease. Identification of gene(s), as part of the etiology of Parkinson’s disease, within the large number of genes residing in these loci can be achieved through several approaches, including screening methods, and considering appropriate criteria.
Idiopathic Parkinson’s disease (PD) is an age-dependent, neurodegenerative
disorder and is predominantly sporadic. Only 20–30% of patients have a positive
family history for PD with a complex mode of inheritance. In a few
extended families, the disease is inherited as an autosomal dominant trait. Linkage
to chromosome 4 was reported in a large Italian kindred multiply affected
by an early-onset form of PD (1). However, this finding was not replicated in a
sample of 94 Caucasian families by Scott et al. (2), or in 13 multigenerational
families by Gasser et al. (3)....
The accumulation of misfolded proteins in the cytosol and nucleus of
neuronal cells leads to neurodegenerative disorders. Polyglutamine diseases
are caused by polyglutamine-expanded proteins, whereas mutations in
superoxide dismutase 1 lead to amyotrophic lateral sclerosis.
Autophagy is a nonspecific bulk degradation pathway for long-lived cyto-plasmic proteins, protein complexes, or damaged organelles. This process is
also a major degradation pathway for many aggregate-prone, disease-cau-sing proteins associated with neurodegenerative disorders, such as mutant
huntingtin in Huntington’s disease. I
Prion diseases are neurodegenerative disorders which cause Creutzfeldt–
Jakob disease in humans, scrapie in sheep and bovine spongiform
encephalopathy in cattle. The infectious agent is a protease resistant iso-form (PrP
) of a host encoded prion protein (PrP
characterized according to size and glycoform pattern.
Prion diseases are fatal neurodegenerative disorders caused by proteina-ceous infectious pathogens termed prions (PrP
). To date, there is no pro-phylaxis or therapy available for these transmissible encephalopathies.
Passive immunization with monclonal antibodies recognizing the normal
host-encoded prion protein (PrP
) has been reported to abolish PrP
infec-tivity and to delay onset of disease.