Neuropathology of Animal Prion Diseases

Abstract

Transmissible Spongiform Encephalopathies (TSEs) or prion diseases are a fatal group of infectious, inherited and spontaneous neurodegenerative diseases affecting human and animals. They are caused by the conversion of cellular prion protein (PrPC) into a misfolded pathological isoform (PrPSc or prion- proteinaceous infectious particle) that self-propagates by conformational conversion of PrPC. Yet by an unknown mechanism, PrPC can fold into different PrPSc conformers that may result in different prion strains that display specific disease phenotype (incubation time, clinical signs and lesion profile). Although the pathways for neurodegeneration as well as the involvement of brain inflammation in these diseases are not well understood, the spongiform changes, neuronal loss, gliosis and accumulation of PrPSc are the characteristic neuropathological lesions. Scrapie affecting small ruminants was the first identified TSE and has been considered the archetype of prion diseases, though atypical and new animal prion diseases continue to emerge highlighting the importance to investigate the lesion profile in naturally affected animals. In this report, we review the neuropathology and the neuroinflammation of animal prion diseases in natural hosts from scrapie, going through the zoonotic bovine spongiform encephalopathy (BSE), the chronic wasting disease (CWD) to the newly identified camel prion disease (CPD).

microRNA-146a-5p, Neurotropic Viral Infection and Prion Disease (PrD)

“…Amongst these brain-and CNS-expressed microRNAs, one of the most well-studied microRNA species known to be involved in the pathogenesis of progressive, age-related neurological diseases is an inducible Homo sapiens microRNA-146a-5p (hsa-miRNA-146a-5p; hsa-miRNA-146a; or simply miRNA-146a) whose significant upregulation is currently implicated in every prion disease (PrD) in humans and animals analyzed to date [12][13][14] (see below); in at least 18 viral-induced encephalopathies, Alzheimer's disease (AD) [15][16][17] and multiple neurological disorders that include cerebrovascular disease (CVD) [3,18], traumatic brain injury (TBI) [19], temporal lobe epilepsy (TLE) [20], age-related macular degeneration (AMD) [10,11,21,22], amyotrophic lateral sclerosis (ALS) [3,23], peripheral neuropathies and neurological tumors of the CNS [3] and neuro-immune diseases such as myasthenia gravis (MG) and multiple sclerosis (MS) [24] (Table 1).…”

Selective Breeding for Disease-Resistant PRNP Variants to Manage Chronic Wasting Disease in Farmed Whitetail Deer

“…This misfolded prion protein is a conformer of a normal cellular prion protein, PrP C , a~250 amino acid protein encoded by a single-copy gene (PRNP) that has been reported in a broad range of mammalian, avian, reptilian, amphibian, and piscine species [8,9]. Despite the wide prevalence of the PRNP gene and PrP C in animal species, TSEs have so far only been reported in humans and ungulates, occasionally spilling over into carnivores [10][11][12][13][14][15][16][17][18].…”

Virus Infection, Genetic Mutations, and Prion Infection in Prion Protein Conversion

“…BSE is an acquired animal prion disease in cattle spread through contaminated meatand-bone meals since the mid-1980s [12]. Transmissible mink encephalopathy in minks, chronic wasting disease (CWD) in deer, and feline spongiform encephalopathy in cats also acquired prion diseases [13,14]. Scrapie is a sporadic animal prion disease in sheep [13].…”

“…Transmissible mink encephalopathy in minks, chronic wasting disease (CWD) in deer, and feline spongiform encephalopathy in cats also acquired prion diseases [13,14]. Scrapie is a sporadic animal prion disease in sheep [13]. Unlike the case of BSE, epidemiological studies suggest unlikelihood of the zoonotic transmissions of scrapie or CWD to humans [15][16][17][18][19].…”