disease

1. 1 Prion disease
A prion is a protein that changes its three-dimensional shape, which can cause disease. Prions
are found in the brain and are resistant to proteases. The function of prions is not fully
understood, but they are believed to play a role in intracellular signaling and cell adhesion
Prion disease represents a group of conditions that affect the nervous system in humans and
animals. In people, these conditions impair brain function, causing changes in memory,
personality, and behavior; a decline in intellectual function (dementia); and abnormal
movements, particularly difficulty with coordinating movements (ataxia). The signs and
symptoms of prion disease typically begin in adulthood and worsen with time, leading to death
within a few months to several years.
Prion diseases or transmissible spongiform encephalopathies (TSEs) are a
family of rare progressive neurodegenerative disorders that affect both
humans and animals. They are distinguished by long incubation periods,
characteristic spongiform changes associated with neuronal loss, and a
failure to induce inflammatory response.
The causative agents of TSEs are believed to be prions. The term “prions”
refers to abnormal, pathogenic agents that are transmissible and are able to
induce abnormal folding of specific normal cellular proteins called prion
proteins that are found most abundantly in the brain. The functions of these
normal prion proteins are still not completely understood. The abnormal
folding of the prion proteins leads to brain damage and the characteristic
signs and symptoms of the disease. Prion diseases are usually rapidly
progressive and always fatal.
A prion is composed of an abnormally folded protein that causes
progressive neurodegenerative conditions, with two of the most notable
being Bovine spongiform encephalopathy (BSE or mad cow disease) seen
in cattle and livestock and Creutzfeldt-Jakob disease (CJD) seen in humans.
The most likely infection route of the acquired prion diseases is via oral intake and what follows is an
accumulation and amplification of prion infectivity in lymphoid tissues associated with the gut.
Prions are self-propagating protein aggregates that act as protein-based elements of inheritance in
fungi. Unlike other infectious agents, such as bacteria, viruses, and fungi, prions do not contain
genetic materials such as DNA or RNA. The unique traits and genetic information of prions are
believed to be encoded within the conformational structure and posttranslational modifications of the
proteins
Causes

2. Between 10 and 15 percent of all cases of prion disease are caused by mutations in the PRNP gene.
Because they can run in families, these forms of prion disease are classified as familial. Familial prion
diseases, which have overlapping signs and symptoms, include familial Creutzfeldt-Jakob disease (CJD),
Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI)
Frequency
These disorders are very rare. Although the exact prevalence of prion disease is unknown, studies
suggest that this group of conditions affects about one person per million worldwide each year.
Approximately 350 new cases are reported annually in the United States.
Description
Prion disease represents a group of conditions that affect the nervous system in humans and animals. In
people, these conditions impair brain function, causing changes in memory, personality, and behavior; a
decline in intellectual function (dementia); and abnormal movements, particularly difficulty with
coordinating movements (ataxia). The signs and symptoms of prion disease typically begin in adulthood
and worsen with time, leading to death within a few months to several years.
Inheritance
Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy
of the altered PRNP gene in each cell is sufficient to cause the disorder. In most cases, an affected person
inherits the altered gene from one affected parent. In some people, familial forms of prion disease are
caused by a new mutation in the gene that occurs during the formation of a parent's reproductive cells
(eggs or sperm) or in early embryonic development. Although such people do not have an affected
parent, they can pass the genetic change to their children.
The sporadic, acquired, and iatrogenic forms of prion disease, including kuru and variant Creutzfeldt-
Jakob disease, are not inherited.
Other Names for This Condition
Inherited human transmissible spongiform encephalopathies
Prion protein diseases
Prion-associated disorders
Prion-induced disorders
Transmissible dementias
Transmissible spongiform encephalopathies
TSEs
What is the mechanism of prion disease?

3. Prion diseases are a group of infectious neurodegenerative diseases with an entirely novel mechanism of
transmission, involving a protein-only infectious agent that propagates the disease by transmitting
protein conformational changes. The disease results from extensive and progressive brain degeneration.
Human Prion Diseases
• Creutzfeldt-Jakob Disease (CJD)
• Variant Creutzfeldt-Jakob Disease (vCJD)
• Gerstmann-Straussler-Scheinker Syndrome
• Fatal Familial Insomnia
• Kuru
Animal Prion Diseases
• Bovine Spongiform Encephalopathy (BSE)
• Chronic Wasting Disease (CWD)
• Scrapie
• Transmissible mink encephalopathy
• Feline spongiform encephalopathy
• Ungulate spongiform encephalopathy
immunoresponsethe
2 THE Innate immune system ;
Prion infection does not elicit any detectable specific humoral or
cellular immunoresponse, but host innate immunity appears to be
persistently activated in infected brains, possibly for clearance of
prions. Accumulated scrapie-like prion protein (PrPSc) may further
stimulate strong non-specific
• Prion diseases occur when normal prion protein, found on the surface
of many cells, becomes abnormal and clump in the brain, causing brain
damage. This abnormal accumulation of protein in the brain can cause
memory impairment, personality changes, and difficulties with
After infection, the targeting of peripherally-acquired prions to specific
immune cells in the secondary lymphoid organs (SLO), such as the lymph

4. nodes and spleen, is essential for the efficient transmission of disease to the
brain
Prion diseases are a unique group of infectious chronic neurodegenerative
disorders to which there are no cures. Although prion infections do not
stimulate adaptive immune responses in infected individuals, the actions of
certain immune cell populations can have a significant impact on disease
pathogenesis. After infection, the targeting of peripherally-acquired prions to
specific immune cells in the secondary lymphoid organs (SLO), such as the
lymph nodes and spleen, is essential for the efficient transmission of disease
to the brain. Once the prions reach the brain, interactions with other
immune cell populations can provide either host protection or accelerate the
neurodegeneration. In this review, we provide a detailed account of how
factors such as inflammation, ageing and pathogen co-infection can affect
prion disease pathogenesis and susceptibility. For example, we discuss how
changes to the abundance, function and activation status of specific immune
cell populations can affect the transmission of prion diseases by peripheral
routes. We also describe how the effects of systemic inflammation on certain
glial cell subsets in the brains of infected individuals can accelerate the
neurodegeneration. A detailed understanding of the factors that affect prion
disease transmission and pathogenesis is essential for the development of
novel intervention strategies.
prions and prion disease, immune system, inflammation, aging, co-infection,
susceptibility
the immune system deal with prions;Surprisingly, the immune system
appears to behave as a Trojan's horse rather than a protective fortification
during prion infections. Because prions seem to be essentially composed of a
protein, PrP(Sc), identical in sequence to a host encoded protein, PrP(C), the
spe efficient transmission of disease to the brain
The part of the immune system fights prions;After infection, the targeting of
peripherally-acquired prions to specific immune cells in the secondary
lymphoid organs (SLO), such as the lymph nodes and spleen, is essential for
thecific immune system displays a natural tolerance.

5. the type of cells do prions infect;Several cell types are thought to produce
PrPSc following prion infection in vivo, including neurons, astrocytes, and
lymphoreticular cells (9, 49, 53, 134).
the role of prion protein in immune system;It is up-regulated in T cell
activation and may be expressed at higher levels by specialized classes of
lymphocyte. Furthermore, antibody cross-linking of surface PrP modulates T
cell activation and leads to rearrangements of lipid raft constituents and
increased phosphorylation of signalling proteins. Prion diseases are a unique
group of infectious chronic neurodegenerative disorders to which there are
no cures. Although prion infections do not stimulate adaptive immune
responses in infected individuals, the actions of certain immune cell
populations can have a significant impact on disease pathogenesis.