Degenerative Diseases of the Nervous System
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
Additional pathologic findings may include the following: Lewy body–related neurites: found by means of ubiquitin staining in the hippocampus (CA2–3 region), amygdala, nucleus basalis of Meynert, dorsal vagal nucleus, and other brainstem nuclei. They are a neurofilament abnormality in which the proteins are present as a diffuse aggregate that does not contain crystallin.Plaques (all morphologic types). Senile neuritic plaques, often in similar numbers to those found in AD, and Aβ deposition are common.Neocortical NFTs are few or absent.Regional neuronal loss occurs, particularly in brainstem (substantia nigra and locus ceruleus) and nucleus basalis of Meynert.Microvacuolation (spongiform change) and synapse loss.Neurochemical abnormalities and neurotransmitter deficits.
The Pineal Gland
Nate F. Cardarelli in The Thymus in Health and Senescence, 2019
A number of cell culture studies provide data indicating pineal-retina similarities. It is known that nonlenticular cells of vertebrate eyes will transdifferentiate into lens cells in vitro.232 Lens cells are never found in the pineal in situ. However, pinealocytes from 8-d-old quail embryos cultured for prolonged periods (over 4 weeks) will transdifferentiate into retina-like cells resembling the “lentoid bodies” of cultured ocular cells.233 δ-Crystallin has been found in both the pineal and retina cells when extirpated and is produced in tissue cultures of both.233,234 Most interestingly, δ-crystallin is also found in the limb bud cells of chick embryos in vitro.234 The transdifferentiation becomes noticeable on the 5th day in culture. Of course, limb bud cells never form lens structures. The meaning is not clear unless the substance plays a role in growth regulation. Thaller and Eichele, in a recent report, note that the limb bud of stage-21 embryos contains endogenous retinoic acid,235 thus showing another link between rapidly growing embryonic tissue and the retina.
Translation and Post-Translational Modifications During Aging
Alvaro Macieira-Coelho in Molecular Basis of Aging, 2017
It has also been suggested that the loss of 11 lysine residues, presumed due to oxidation, may be the cause of the inactivation of 6-phosphogluconate dehydrogenase in rat livers and human erythrocytes during aging. Similarly, the loss of activity of rat liver malic enzyme during aging is related to the loss of histidine residues by oxidation.146 Furthermore, oxidation of a cysteine residue in glyceraldehyde-3-phosphate dehydrogenase may be responsible for its inactivation during aging in rat muscles.147,148 It has also been reported that the concentration of the oxidation products of human lens proteins and skin collagen increases along with the accumulation of oxidative forms of α-crystallin in patients with age-related cataracts.140 However, the content of ortho-tyrosine and dityrosine, formed by the oxidation of phenylalanine and tyrosine, respectively, did not increase in the aging human lens.149
Crocin as a vision supplement
Published in Clinical and Experimental Optometry, 2023
Mojtaba Heydari, Mousa zare, Mohammad Reza Badie, Ronald Ross Watson, Mohammad Reza Talebnejad, Mehrdad Afarid
Cataract is the leading cause of blindness worldwide.47 Surgical management is the only current option for the treatment of cataracts. In this respect, medical treatments have been investigated for the prevention and treatment of cataracts.48 Bahmani et al.49 evaluated the preventive effect of intraperitoneal crocin on the α-crystallin glycation-induced cataract in an animal model. α-crystallin is a protein that helps to maintain the transparency of the eye lens. The compromised function of α-crystallin by glycation can result in cataract formation in ageing and diabetes. Cross-linking of crystalline lens proteins is known as causative factor for cataract formation. Increased hydrophobicity and decreased solubility of these proteins is another factor associated with lens opacity and cataract. Bahmani et al.49 observed that crocin inhibited advanced glycation end product, protein cross-linking, and hydrophobicity in the experimental model of streptozotocin-induced diabetes.
A Review of Lens Biomechanical Contributions to Presbyopia
Published in Current Eye Research, 2023
Intact α-crystallin appears to be more common toward the exterior of the lens and in the cortex. Differing isoforms and degradation products associated with α-crystallin are more prevalent toward the center of the lens.103,104 The apparent gradient of intact to degraded crystallin protein from the exterior to interior of the lens may be explained by the concentric lens growth pattern as LECs differentiate into fiber cells which stack on existing layers compacting their substrate. Aged proteins thus accumulate toward the lens nucleus as fresh protein is deposited in new cortical fiber cell layers.122 This is not the only potential factor which could lead to a protein degradation gradient through the lens, nor is this phenomenon exclusive to α-crystallin. Numerous factors could alter protein stability in the lens at varying depths. Exposure to reactive oxygen species which can cause protein crosslinking1 may be more likely in cortical cells. Diffusion may be altered spatially within the lens. Microcirculation, which can import beneficial chemicals such as antioxidants and glutathione123 may be reduced in the lens interior. Cells may be subject to greater strain applied by the capsule during accommodation at different lenticular locations.
Endoplasmic reticulum stress as an underlying factor in leading causes of blindness and potential therapeutic effects of 4-phenylbutyric acid: from bench to bedside
Published in Expert Review of Ophthalmology, 2022
Sahar Askari, Fatemeh Azizi, Pegah Javadpour, Nasser Karimi, Rasoul Ghasemi
Crystallin is one of the lens’ structural proteins fundamental for lens transparency. Its mutations lead to structural and functional changes in the lens structure and the development of cataracts. In one in vitro investigation, 4-PBA with chaperoning properties reduced apoptosis, possibly by reversing the defective phenotype of the protein [120]. In addition, 4-PBA is able to keep HLECs from morphological changes by suppressing ER stress and regulating EMT after cataract surgery [30]. Another study that administered 4-PBA orally to galactose-fed rats (as a model of diabetic cataract) demonstrated that treatment with 4-PBA suppressed LECs death by decreasing ER stress markers, which partially delayed cataract formation [128]. In another study, it was established that 4-PBA is able to improve cataracts in diabetic rats. In details, by 4-PBA treatment, alteration of protein profile in the lenses of diabetic model rats was retarded as most of the control rat eyes. In line with these clinical findings, examination of lens histopathology also confirmed the potential utility of 4-PBA in diabetic animals cataract [129].